greenmedinfo--2020-12-19--Radiation-induced bystander effects may contribute to radiation-induced cognitive impairment.

PURPOSE : Despite being a major treatment modality for brain cancer due to its efficiency in achieving cancer control , radiotherapy has long been known to cause long-term side effects , including radiation-induced cognitive impairment ( RICI ) .
Neurogenesis inhibition due to radiation-induced damage in neural stem cells ( NSCs ) has been demonstrated to be an important mechanism underlying RICI .
Radiation-induced bystander effects ( RIBEs ) denote the biological responses in non-targeted cells after their neighbouring cells are irradiated .
We have previously demonstrated that RIBEs could play an important role in the skin wound healing process @ @ @ @ @ @ @ whether RIBEs contribute to RICI in this study .
MATERIALS AND METHODS : The transwell co-culture method was used to investigate bystander effects in mouse NSCs induced by irradiated GL261 mouse glioma cells in vitro .
The proliferation , neurosphere-forming capacity and differentiation potential of NSCs were determined as the bystander endpoints .
The exosomes were extracted from the media used to culture GL261 cells and were injected into the hippocampus of C57BL/6 mice .
Two months later , the neurogenesis of mice was assessed using BrdU incorporation and immunofluorescence microscopy , and @ @ @ @ @ @ @ Water Maze .
RESULTS : After co-culture with GL261 glioma cells , mouse NSCs displayed inhibited proliferation and reduced neurosphere-forming capacity and differentiation potential .
The irradiated GL261 cells caused greater inhibition and reduction in NSCs than unirradiated GL261 cells .
Moreover , adding the exosomes secreted by GL261 cells into the culture of NSCs inhibited NSC proliferation , suggesting that the cancer cell-derived exosomes may be critical intercellular signals .
Furthermore , injection of the exosomes from GL261 cells into the hippocampus of mice caused significant neurogenesis inhibition and cognitive impairment two @ @ @ @ @ @ @ irradiated GL261 cells induced greater inhibitory effects .
CONCLUSION : RIBEs mediated by the exosomes from irradiated cancer cells could contribute to RICI and , therefore , could be a novel mechanism underlying RICI .

PURPOSE: Despite being a major treatment modality for brain cancer due to its efficiency in achieving cancer control, radiotherapy has long been known to cause long-term side effects, including radiation-induced cognitive impairment (RICI). Neurogenesis inhibition due to radiation-induced damage in neural stem cells (NSCs) has been demonstrated to be an important mechanism underlying RICI. Radiation-induced bystander effects (RIBEs) denote the biological responses in non-targeted cells after their neighbouring cells are irradiated. We have previously demonstrated that RIBEs could play an important role in the skin wound healing process. Therefore, we aimed to investigate whether RIBEs contribute to RICI in this study.
MATERIALS AND METHODS: The transwell co-culture method was used to investigate bystander effects in mouse NSCs induced by irradiated GL261 mouse glioma cells in vitro. The proliferation, neurosphere-forming capacity and differentiation potential of NSCs were determined as the bystander endpoints. The exosomes were extracted from the media used to culture GL261 cells and were injected into the hippocampus of C57BL/6 mice. Two months later, the neurogenesis of mice was assessed using BrdU incorporation and immunofluorescence microscopy, and cognitive function was evaluated by the Morris Water Maze.
RESULTS: After co-culture with GL261 glioma cells, mouse NSCs displayed inhibited proliferation and reduced neurosphere-forming capacity and differentiation potential. The irradiated GL261 cells caused greater inhibition and reduction in NSCs than unirradiated GL261 cells. Moreover, adding the exosomes secreted by GL261 cells into the culture of NSCs inhibited NSC proliferation, suggesting that the cancer cell-derived exosomes may be critical intercellular signals. Furthermore, injection of the exosomes from GL261 cells into the hippocampus of mice caused significant neurogenesis inhibition and cognitive impairment two month later, and the exosomes from irradiated GL261 cells induced greater inhibitory effects.
CONCLUSION: RIBEs mediated by the exosomes from irradiated cancer cells could contribute to RICI and, therefore, could be a novel mechanism underlying RICI.


greenmedinfo--2020-12-19--Grape seed proanthocyanidin extract supplementation alleviates DSS-induced colitis.

It is widely believed that grape seed proanthocyanidin extract ( GSPE ) exerts antioxidant and anti-inflammatory effects .
Dietary supplementation with GSPE has been reported to alleviate colitis signs in mice , but the mechanisms involved require further exploration .
The present study investigated how the oral administration of GSPE ameliorates colitis signs and reduces colitis-associated inflammation .
C57BL/6 mice were treated with GSPE for 21 days .
During the final 7 days of treatment , the mice were administered dextran sulfate sodium ( DSS ) dissolved in drinking water to induce experimental colitis .
We found that GSPE treatment @ @ @ @ @ @ @ by decreases in disease activity index ( DAI ) scores , pathological scores , and oxidative stress and increases in zonula occludens-1 ( ZO-1 ) , occludin , and claudin-1 mRNA levels of colon tissue .
Notably , the proinflammatory cytokines TNF-α and IL-1β were significantly downregulated as a result of GSPE treatment in colon tissues .
GSPE treatment also reduced NLR family pyrin domain-containing 3 ( NLRP3 ) inflammasome mRNA levels of colon tissue .
Furthermore , an analysis of 16S rRNA sequences showed that GSPE rebalanced the DSS-damagedgut microbiota , including @ @ @ @ @ @ @ , increasing Verrucomicrobia and Akkermansia , and elevating the Firmicutes to Bacteroidetes ratio .
In conclusion , GSPE supplementation alleviates DSS-induced colitis by modulating inflammatory cytokines and oxidation stress , maintaining the intestinal barrier , and improving the microbial community .
These results indicate that GSPE might be a new dietary strategy for the treatment of ulcerative colitis .

It is widely believed that grape seed proanthocyanidin extract (GSPE) exerts antioxidant and anti-inflammatory effects. Dietary supplementation with GSPE has been reported to alleviate colitis signs in mice, but the mechanisms involved require further exploration. The present study investigated how the oral administration of GSPE ameliorates colitis signs and reduces colitis-associated inflammation. C57BL/6 mice were treated with GSPE for 21 days. During the final 7 days of treatment, the mice were administered dextran sulfate sodium (DSS) dissolved in drinking water to induce experimental colitis. We found that GSPE treatment improved DSS-induced colitis, which was evidenced by decreases in disease activity index (DAI) scores, pathological scores, and oxidative stress and increases in zonula occludens-1 (ZO-1), occludin, and claudin-1 mRNA levels of colon tissue. Notably, the proinflammatory cytokines TNF-α and IL-1β were significantly downregulated as a result of GSPE treatment in colon tissues. GSPE treatment also reduced NLR family pyrin domain-containing 3 (NLRP3) inflammasome mRNA levels of colon tissue. Furthermore, an analysis of 16S rRNA sequences showed that GSPE rebalanced the DSS-damagedgut microbiota, including reducing Bacteroidetes, Dubosiella, and Veillonella, increasing Verrucomicrobia and Akkermansia, and elevating the Firmicutes to Bacteroidetes ratio. In conclusion, GSPE supplementation alleviates DSS-induced colitis by modulating inflammatory cytokines and oxidation stress, maintaining the intestinal barrier, and improving the microbial community. These results indicate that GSPE might be a new dietary strategy for the treatment of ulcerative colitis.


greenmedinfo--2020-12-19--Grape seed extract alleviates radiation-induced damages in human blood lymphocytes.

Objective : Ionizing radiation induces deleterious effects in the biological systems by producing free radicals .
Grape Seed Extract ( GSE ) as a free radical scavenger could protect the body against the damages Materials and Methods : In this study , 12 healthy male volunteers were divided into Groups 1 , 2 , 3 and 4 and received 100 , 300 , 600 and 1000 mg GSE , respectively .
Peripheral blood samples were collected from each volunteer 15 min before , and 1 , 2 , and 5 hr after GSE oral administration .
Blood samples were then @ @ @ @ @ @ @ X-ray ( Irradiated control group , was treated with only 1.5 Gy of X-rays ) .
Cytogenic damages were detected by micronucleus assay .
Results : Results showed that irradiation significantly increased the incidence of micronuclei ( p < 0 .
001 ) .
In group 1 , the mean reduction of micronucleus rate was 26.53 % , 34.92 % , and 31.38 % , 1 , 2 , and 5 hr after GSE ingestion ( p < 0.001 ) , respectively ; this variable in group 2 was 17.38 , 38.33 , @ @ @ @ @ @ @ 001 ) , in group 3 , was 35.65 % , 46 % , and 37.15 % ( p < 0.001 ) , respectively and in group 4 , was 41.35 % , 51.73 % , and 50.55 % ( p < 0.0001 ) , respectively .
The samples collected 1 , 2 , and 5 hr after ingestion of GSE exhibited a significant decrease in the incidence of micronuclei compared with the radiation control group .
The maximum protection and reduction in frequency of micronuclei ( 51.73 % ) was observed 2 @ @ @ @ @ @ @ .
Conclusion : Consumption of GSE before undergoing radiation protects human lymphocytes against X-rays by reducing radiation-induced genotoxicity .

Objective: Ionizing radiation induces deleterious effects in the biological systems by producing free radicals. Grape Seed Extract (GSE) as a free radical scavenger could protect the body against the damages
Materials and Methods: In this study, 12 healthy male volunteers were divided into Groups 1, 2, 3 and 4 and received 100, 300, 600 and 1000 mg GSE, respectively. Peripheral blood samples were collected from each volunteer 15 min before, and 1, 2, and 5 hr after GSE oral administration. Blood samples were then irradiated with 150 cGy of 100 kvp X-ray (Irradiated control group, was treated with only 1.5 Gy of X-rays). Cytogenic damages were detected by micronucleus assay.
Results: Results showed that irradiation significantly increased the incidence of micronuclei (p<0. 001). In group 1, the mean reduction of micronucleus rate was 26.53%, 34.92%, and 31.38%, 1, 2, and 5 hr after GSE ingestion (p<0.001), respectively; this variable in group 2 was 17.38, 38.33, and 31.38 (p<0. 001), in group 3, was 35.65%, 46%, and 37.15% (p<0.001), respectively and in group 4, was 41.35%, 51.73%, and 50.55% (p<0.0001), respectively. The samples collected 1, 2, and 5 hr after ingestion of GSE exhibited a significant decrease in the incidence of micronuclei compared with the radiation control group. The maximum protection and reduction in frequency of micronuclei (51.73%) was observed 2 hr after ingestion of 1000 mg GSE.
Conclusion: Consumption of GSE before undergoing radiation protects human lymphocytes against X-rays by reducing radiation-induced genotoxicity.


greenmedinfo--2020-12-19--Grape seed extract can be used as an effective and sustainable natural resource for prevention of UV

Grape seed extract can be used as an effective and sustainable natural resource for prevention of UV-induced skin damage.

BACKGROUND : Grape seed extract ( GSE ) is rich in polyphenolic compounds , particularly ( + ) -catechin ( C ) and ( - ) -epicatechin ( EC ) .
Strong antioxidant activity of these compounds makes GSE to be value-added to the cosmetics with anti-aging properties .
However , a lack of stability in different environmental conditions makes GSE challenging for the development of photostable cosmetic sunscreen products .
AIMS : To evaluate photoprotective effects of GSE on human dermal fibroblasts irradiated with UVA light and assess photostability of catechins in cream formulations containing GSE alone or in @ @ @ @ @ @ @ .
METHODS : MTT assay was used to assess protective effects of GSE on fibroblasts irradiated with UVA light .
A photostability of C and EC in GSE and in cream formulation containing GSE was investigated using high-performance liquid chromatography and confirmed by reflection and transmission spectrophotometry using Transpore™ tapes and polymethacrylate ( PMMA ) plates as substrates .
RESULTS : High UVA doses damaged fibroblast structure and inhibited their growth .
However , GSE increased cell viability and effectively protected them from UVA damage .
Photostability of C and EC was achieved @ @ @ @ @ @ @ also improved absorption capacity of UV filter and increased overall efficacy of formulation .
PMMA plates showed better applicability for in vitro photostability testing of sunscreen formulations .
However , despite the instability of Transpore® tape under heat from UV exposure , it can still be economically a substrate of alternative choice for screening .
CONCLUSIONS : GSE can be used as an effective and sustainable natural resource for prevention of UV-induced skin damage providing long-term protection against premature skin aging .

BACKGROUND: Grape seed extract (GSE) is rich in polyphenolic compounds, particularly (+)-catechin (C) and (-)-epicatechin (EC). Strong antioxidant activity of these compounds makes GSE to be value-added to the cosmetics with anti-aging properties. However, a lack of stability in different environmental conditions makes GSE challenging for the development of photostable cosmetic sunscreen products.
AIMS: To evaluate photoprotective effects of GSE on human dermal fibroblasts irradiated with UVA light and assess photostability of catechins in cream formulations containing GSE alone or in combination with octyl methoxycinnamate (OMC).
METHODS: MTT assay was used to assess protective effects of GSE on fibroblasts irradiated with UVA light. A photostability of C and EC in GSE and in cream formulation containing GSE was investigated using high-performance liquid chromatography and confirmed by reflection and transmission spectrophotometry using Transpore™ tapes and polymethacrylate (PMMA) plates as substrates.
RESULTS: High UVA doses damaged fibroblast structure and inhibited their growth. However, GSE increased cell viability and effectively protected them from UVA damage. Photostability of C and EC was achieved by combination of GSE and OMC that also improved absorption capacity of UV filter and increased overall efficacy of formulation. PMMA plates showed better applicability for in vitro photostability testing of sunscreen formulations. However, despite the instability of Transpore® tape under heat from UV exposure, it can still be economically a substrate of alternative choice for screening.
CONCLUSIONS: GSE can be used as an effective and sustainable natural resource for prevention of UV-induced skin damage providing long-term protection against premature skin aging.


greenmedinfo--2020-12-19--Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithel

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia.

PURPOSE : To investigate the effects of grape seed proanthocyanidin B2 ( GSPB2 ) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion ( RIR ) .
METHODS : Forty male ICR mice were randomly divided into 4 groups : Group A : mice were treated with right nephrectomy .
Group B : right kidney was resected and the left renal vessel was clamped for 45 minutes .
Group C : mice were intraperitoneally injected with GSPB2 before RIR established .
Group D : mice were intraperitoneally injected with GSPB2 plus brusatol before @ @ @ @ @ @ @ of mice were determined .
Pathological and morphological changes of kidney were checked .
Expressions of Nrf-2 , HO-1 , cleaved-caspase3 were detected by Western-blot .
RESULTS : Compared to Group B , morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B .
The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B .
CONCLUSION : GSPB2 preconditioning could attenuate renal oxidative stress injury and @ @ @ @ @ @ @ expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3 , but the protective effect could be reversed by brusatol .

PURPOSE: To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR).
METHODS: Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot.
RESULTS: Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B.
CONCLUSION: GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.


greenmedinfo--2020-12-19--Vitis vinifera: An alternative for the prevention of neurodegenerative diseases.

To present a systematic review of published studies in databases such as PUBMED , REDALYC , SCIELO , DIALNET , SCOPUS , EBSCO and CONRICYT related to the role-played by the components present in the vegetable oil of grape seed ( Vitis vinífera ) and the prevention or delay in the onset or progression of neurodegenerative diseases .
The analysis of the research revealed that neurodegenerative diseases causes alterations in consciousness or in the nervous system leading to severe damage in neuronal cells , these pathologies are considered gradual and progressive .
Various syndromes manifest the degenerative diseases of the @ @ @ @ @ @ @ the predominant symptom is the progressive dementia .
Among the components of the diet that in numerous epidemiological studies have shown an inverse association are vitamins , minerals , carotenoids , polyunsaturated fatty acids and polyphenols , the latter being the ones addressed in this document .
There is an important evidence that a nutritional support based on polyunsaturated fatty acids and antioxidants can be applied to subjects with a history of neurodegenerative conditions in order to act as neuroprotectors .
This requires the determination of the nutritional benefits of these nutrients or @ @ @ @ @ @ @ group of patients .

To present a systematic review of published studies in databases such as PUBMED, REDALYC, SCIELO, DIALNET, SCOPUS, EBSCO and CONRICYT related to the role-played by the components present in the vegetable oil of grape seed (Vitis vinífera) and the prevention or delay in the onset or progression of neurodegenerative diseases. The analysis of the research revealed that neurodegenerative diseases causes alterations in consciousness or in the nervous system leading to severe damage in neuronal cells, these pathologies are considered gradual and progressive. Various syndromes manifest the degenerative diseases of the nervous system; in some of them the predominant symptom is the progressive dementia. Among the components of the diet that in numerous epidemiological studies have shown an inverse association are vitamins, minerals, carotenoids, polyunsaturated fatty acids and polyphenols, the latter being the ones addressed in this document. There is an important evidence that a nutritional support based on polyunsaturated fatty acids and antioxidants can be applied to subjects with a history of neurodegenerative conditions in order to act as neuroprotectors. This requires the determination of the nutritional benefits of these nutrients or of nutraceuticals for the health of this group of patients.


greenmedinfo--2020-12-19--The effect of grape products containing polyphenols on C-reactive protein levels.

Although grape polyphenols can decrease chronic inflammations , their effect on C-reactive protein ( CRP ) levels is still controversial .
So , this meta-analysis was conducted to investigate the effect of grape products containing polyphenols on CRP concentrations .
In order to collect the relevant randomized controlled trials ( RCTs ) , the data bases of PubMed , Scopus , Web of Science , and Google Scholar were searched up to March 30 , 2020 .
The random-effects model , standardized mean difference , and 95 % confidence interval were applied in data analysis .
Meta-analysis was conducted over @ @ @ @ @ @ @ 668 participants .
The study registration number is CRD42018110169 .
Based on the results , grape products containing polyphenol decreased the CRP levels significantly ( SMD = -0.229 ; 95 % CI : -0.41 , -0.05 ; P = 0.013 ) .
The sensitivity analysis was performed by removing each individual study and the results did not change .
According to the subgroup analysis , higher doses of grape polyphenols ( ˃ 500 mg/d ) and longer intervention periods ( ≥ 12 wk ) had significant effects on CRP levels .
Furthermore , @ @ @ @ @ @ @ in patients with a clinical condition .
In the same vein , grape seed extract and other grape products , such as grape extract , juice , andraisin , decreased the CRP levels significantly .
According to the meta-regression results , the CRP level depends on the dose and duration of the grape polyphenols supplementation .
Based on the findings , grape products containing polyphenols had a significant effect on CRP levels .
Further well-designed and long-term clinical trials are highly recommended to achieve more comprehensive and accurate results .

Although grape polyphenols can decrease chronic inflammations, their effect on C-reactive protein (CRP) levels is still controversial. So, this meta-analysis was conducted to investigate the effect of grape products containing polyphenols on CRP concentrations. In order to collect the relevant randomized controlled trials (RCTs), the data bases of PubMed, Scopus, Web of Science, and Google Scholar were searched up to March 30, 2020. The random-effects model, standardized mean difference, and 95% confidence interval were applied in data analysis. Meta-analysis was conducted over 17 eligible RCTs containing a total of 668 participants. The study registration number is CRD42018110169. Based on the results, grape products containing polyphenol decreased the CRP levels significantly (SMD = -0.229; 95% CI: -0.41, -0.05; P = 0.013). The sensitivity analysis was performed by removing each individual study and the results did not change. According to the subgroup analysis, higher doses of grape polyphenols (˃ 500 mg/d) and longer intervention periods (≥ 12 wk) had significant effects on CRP levels. Furthermore, grape polyphenols significantly reduced the CRP levels in patients with a clinical condition. In the same vein, grape seed extract and other grape products, such as grape extract, juice, andraisin, decreased the CRP levels significantly. According to the meta-regression results, the CRP level depends on the dose and duration of the grape polyphenols supplementation. Based on the findings, grape products containing polyphenols had a significant effect on CRP levels. Further well-designed and long-term clinical trials are highly recommended to achieve more comprehensive and accurate results.


greenmedinfo--2020-12-19--Effects of acute grape seed extract supplementation on hemodynamics in normal body weight and obese

Effects of acute grape seed extract supplementation on hemodynamics in normal body weight and obese males.

Recently , it has been reported that dietary supplementation with grape seed extract ( GSE ) ameliorates endothelial function and increase nitric oxide ( NO ) bioavailability .
Thus , we investigated if elevated blood pressure and aortic stiffness ( AoS ) characterized in obese individuals are attenuated following acute GSE supplementation .
Twenty men ( obese=10 ; normal body weight ( NBW ) =10 ) participated in this study .
Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) , mean arterial pressure ( MAP ) , heart rate ( HR ) , stroke volume @ @ @ @ @ @ @ CO ) , total peripheral resistance ( TPR ) , and AoS were compared 2 h after ingestion of GSE or placebo ( PL ) on different days , 1 wk apart .
Compared with the PL , GSE supplementation significantly decreased SBP ( NBW : 103±4 vs. 99±3 mmHg ; obese : 118±3 vs. 112±5 mmHg ) and MAP ( NBW : 75±2 vs. 72±2 mmHg ; obese : 86±3 vs. 84±3 mmHg ) in both groups , while there were no differences in HR , SV , DBP , TPR , @ @ @ @ @ @ @ CO in only obese group .
In NBW group , TPR tended to be decreased , but there was no significant difference .
Our study suggests that acute supplementation with GSE reduced both SBP and MAP via a reduction in CO in obese individuals and decreased peripheral vasoconstriction in NBW group .

Recently, it has been reported that dietary supplementation with grape seed extract (GSE) ameliorates endothelial function and increase nitric oxide (NO) bioavailability. Thus, we investigated if elevated blood pressure and aortic stiffness (AoS) characterized in obese individuals are attenuated following acute GSE supplementation. Twenty men (obese=10; normal body weight (NBW)=10) participated in this study. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), and AoS were compared 2 h after ingestion of GSE or placebo (PL) on different days, 1 wk apart. Compared with the PL, GSE supplementation significantly decreased SBP (NBW: 103±4 vs. 99±3 mmHg; obese: 118±3 vs. 112±5 mmHg) and MAP (NBW: 75±2 vs. 72±2 mmHg; obese: 86±3 vs. 84±3 mmHg) in both groups, while there were no differences in HR, SV, DBP, TPR, and AoS. GSE supplementation significantly decreased CO in only obese group. In NBW group, TPR tended to be decreased, but there was no significant difference. Our study suggests that acute supplementation with GSE reduced both SBP and MAP via a reduction in CO in obese individuals and decreased peripheral vasoconstriction in NBW group.


greenmedinfo--2020-12-19--Grape seed procyanidins suppress the apoptosis and senescence of chondrocytes and ameliorates osteoa

Grape seed procyanidins suppress the apoptosis and senescence of chondrocytes and ameliorates osteoarthritis.

Osteoarthritis ( OA ) is a complicated pathological condition affecting thousands of people around world , many with substantial unmet medical care needs and without any effective therapies .
Previous study has indicated that glucagon-like peptide-1 ( GLP-1 ) is involved in the pathological progress of osteoarthritis ; however , the role of dipeptidase-4 ( DPP4 ) , which regulates the degradation of GLP-1 , still remains unclear in osteoarthritis .
Herein , after comparing normal mouse cartilage tissues with OA mouse cartilage tissues by histological analysis , we found out that DPP4 was highly expressed in OA cartilage tissues @ @ @ @ @ @ @ in osteoarthritis , the apoptosis and senescence of chondrocytes were found to be decreased in vitro when DPP4 was downregulated by siRNA in chondrocytes .
Further study showed that the inhibition of DPP4 by procyanidins , a grape seed extract , attenuated apoptosis and senescence of chondrocytes in vitro .
Furthermore , the results showed that DPP4 inhibition protects cartilage by activating Sirt1 , which has been reported to be associated with many pathophysiological processes , particularly in age-related diseases , such as neurodegenerative disorders and osteoarthritis .
In addition , animal experiment @ @ @ @ @ @ @ ameliorating the progression of osteoarthritis through the inhibition of DPP4 .
This study provides a competitive target for the therapeutic treatment of osteoarthritis , and procyanidins were shown to be a potential medicine for the restoration of the effects of osteoarthritis .

Osteoarthritis (OA) is a complicated pathological condition affecting thousands of people around world, many with substantial unmet medical care needs and without any effective therapies. Previous study has indicated that glucagon-like peptide-1 (GLP-1) is involved in the pathological progress of osteoarthritis; however, the role of dipeptidase-4 (DPP4), which regulates the degradation of GLP-1, still remains unclear in osteoarthritis. Herein, after comparing normal mouse cartilage tissues with OA mouse cartilage tissues by histological analysis, we found out that DPP4 was highly expressed in OA cartilage tissues. To investigate the role of DPP4 in osteoarthritis, the apoptosis and senescence of chondrocytes were found to be decreased in vitro when DPP4 was downregulated by siRNA in chondrocytes. Further study showed that the inhibition of DPP4 by procyanidins, a grape seed extract, attenuated apoptosis and senescence of chondrocytes in vitro. Furthermore, the results showed that DPP4 inhibition protects cartilage by activating Sirt1, which has been reported to be associated with many pathophysiological processes, particularly in age-related diseases, such as neurodegenerative disorders and osteoarthritis. In addition, animal experiment results demonstrated that procyanidins were capable of ameliorating the progression of osteoarthritis through the inhibition of DPP4. This study provides a competitive target for the therapeutic treatment of osteoarthritis, and procyanidins were shown to be a potential medicine for the restoration of the effects of osteoarthritis.


greenmedinfo--2020-12-19--Grape seed extract treatment may serve as a potential therapeutic agent in carbamazepine-induced hep

Grape seed extract treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.

Aim : This study investigated the effects of co-administration of carbamazepine ( CBZ ) with grape ( ) seed methanolic extract ( GSME ) on liver toxicity .
Method : Thirty-five male rats ( 145-155 g ) were randomized into 5 groups ( n = 7 ) and administered with propylene glycol ( PG 0.1 mL/day ) , CBZ ( 25 mg/kg ) , CBZ ( 25 mg/kg ) + GSME ( 200 mg/kg ) , CBZ ( 25 mg/kg ) + GSME ( 100 mg/kg ) , or CBZ ( 25 mg/kg ) + GSME ( 50 mg/kg ) @ @ @ @ @ @ @ after the last dose , changes in the body weights were determined .
The rats were euthanized by cervical dislocation .
The liver was weighed and later homogenized ; while the supernatant was analyzed biochemically .
The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation .
Result : There was significant ( p = 0.0001 ) decrease in the body weight following carbamazepine treatment .
The relative liver weight also decreased significantly ( p = 0.0004 ) across the treatment group compared with control .
The activities of @ @ @ @ @ @ @ alanine aminotransferase , alkaline phosphatase , and glutathione activities ) , including the concentrations of malondialdehyde , increased significantly ( p≤ 0.0004 ) following carbamazepine treatment .
Various morphological alterations were observed , especially in the photomicrograph of the CBZ treated rats .
However , these derangements were attenuated significantly in the CBZ - GSME co-treated group .
Conclusion : This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction .

Aim: This study investigated the effects of co-administration of carbamazepine (CBZ) with grape () seed methanolic extract (GSME) on liver toxicity.
Method: Thirty-five male rats (145-155 g) were randomized into 5 groups (n = 7) and administered with propylene glycol (PG 0.1 mL/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) orally for 28 days. Twenty-four hours after the last dose, changes in the body weights were determined. The rats were euthanized by cervical dislocation. The liver was weighed and later homogenized; while the supernatant was analyzed biochemically. The liver tissues were preserved in 10 % neutral-buffered formalin for the histomorphological investigation.
Result: There was significant (p = 0.0001) decrease in the body weight following carbamazepine treatment. The relative liver weight also decreased significantly (p = 0.0004) across the treatment group compared with control. The activities of the liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and glutathione activities), including the concentrations of malondialdehyde, increased significantly (p≤ 0.0004) following carbamazepine treatment. Various morphological alterations were observed, especially in the photomicrograph of the CBZ treated rats. However, these derangements were attenuated significantly in the CBZ - GSME co-treated group.
Conclusion: This study concludes that GSME treatment may serve as a potential therapeutic agent in carbamazepine-induced hepatotoxicity/ dysfunction.


greenmedinfo--2020-12-21--An ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in sho

An ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory.

The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo , possibly via blockade of adenosine A2A receptors ( A2AR ) .
The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74 % inhibition at 150 μg/ml and significant A2AR antagonist activity with 98 % inhibition at 300 μg/mL .
A significant adenosine A1 receptor ( A1R ) antagonist activity with 100 % inhibition was observed at 300 μg/mL .
Its effect on learning and @ @ @ @ @ @ @ using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant ( p < 0.001 ) change in recognition index ( RI ) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p.
, respectively , compared to the vehicle control .
In comparison , the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion ; however , it remained insignificant in RI at 200 mg/kg p.o .
Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term @ @ @ @ @ @ @ adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory .

The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 μg/ml and significant A2AR antagonist activity with 98% inhibition at 300 μg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 μg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p<0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory.


greenmedinfo--2020-12-21--These findings demonstrate that Orthosiphon stamineus extracts have antihyperuricemic and nephroprot

These findings demonstrate that Orthosiphon stamineus extracts have antihyperuricemic and nephroprotective effects.

OBJECTIVES : To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia ( HUA ) mice and @ @ @ @ @ METHODS : Orthosiphon stamineus extracts were extracted using 50 % ethanol and enriched using ethyl @ @ @ @ @ UPLC/ESI-MS. A potassium oxonate ( PO ) induced hyperuricemic mouse model was used to evaluate @ @ @ @ @ O. stamineus ethyl acetate extracts ( OSE ) .
KEY FINDINGS : Eight constituents from @ @ @ @ @ treatment ameliorated HUA by regulating key indicators of kidney dysfunction and xanthine oxidase , adenosine @ @ @ @ @ in hyperuricemic mice .
Moreover , in renal histopathology analysis , OSE significantly alleviated kidney @ @ @ @ @ findings demonstrate that OSE has antihyperuricemic and nephroprotective effects on PO-induced HUA mice and those @ @ @ @ @ be a safe and effective agent or functional ingredient for treating HUA .

OBJECTIVES: To investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms.
METHODS: Orthosiphon stamineus extracts were extracted using 50% ethanol and enriched using ethyl acetate, and characterised utilising UPLC/ESI-MS. A potassium oxonate (PO) induced hyperuricemic mouse model was used to evaluate antihyperuricemia and nephroprotective effects of O. stamineus ethyl acetate extracts (OSE).
KEY FINDINGS: Eight constituents from OSE were identified and OSE treatment ameliorated HUA by regulating key indicators of kidney dysfunction and xanthine oxidase, adenosine deaminase activity and urate transporters in hyperuricemic mice. Moreover, in renal histopathology analysis, OSE significantly alleviated kidney injury.
CONCLUSIONS: These findings demonstrate that OSE has antihyperuricemic and nephroprotective effects on PO-induced HUA mice and those results indicate that OSE could be a safe and effective agent or functional ingredient for treating HUA.


greenmedinfo--2020-12-21--Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection throug

Orthosiphon stamineus protects Caenorhabditis elegans against Staphylococcus aureus infection through immunomodulation.

Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains , the identification of alternative therapeutic molecules has become paramount .
Previously , we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds .
One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves ( UE-12 ) that enhanced the survival of infected nematodes without interfering with bacterial growth .
In this study , we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense @ @ @ @ @ @ @ the presence of UE-12 .
Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways .
Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin ( C18H16O7 ) as the possible candidate active molecule contributing to the anti-infective property of UE-12 .
Taken together , these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in @ @ @ @ @ @ @ the immune response of the infected host .

Amidst growing concerns over the spread of antibiotic-resistant Staphylococcus aureus strains, the identification of alternative therapeutic molecules has become paramount. Previously, we utilized a Caenorhabditis elegans-S. aureus screening platform to identify potential anti-infective agents from a collection of natural extracts and synthetic compounds. One of the hits obtained from the screen was the aqueous extract of Orthosiphon stamineus leaves (UE-12) that enhanced the survival of infected nematodes without interfering with bacterial growth. In this study, we used a fluorescent transgenic reporter strain and observed that the repressed expression of the lys-7 defense gene in infected nematodes was restored in the presence of UE-12. Analysis of a selected panel of PMK-1 and DAF-16-regulated transcripts and loss-of-function mutants in these pathways indicates that the protective role of UE-12 is mediated via the p38 MAP kinase and insulin-like signaling pathways. Further analysis of a panel of known bioactive compounds of UE-12 proposed eupatorin (C18H16O7) as the possible candidate active molecule contributing to the anti-infective property of UE-12. Taken together, these findings strongly suggest that the O. stamineus leaf extract is a promising anti-infective agent that confers an advantage in survival against S. aureus infection by modulating the immune response of the infected host.


greenmedinfo--2020-12-21--Orthosiphon diffusus methanol active fraction demonstrated significant hepatoprotection against carb

Orthosiphon diffusus methanol active fraction demonstrated significant hepatoprotection against carbon tetrachloride-induced hepatotoxicity.

ETHNOPHARMACOLOGICAL RELEVANCE : Preparations of Orthosiphon diffusus ( Benth . )
have been used by folk medicinal practitioners in the Western Ghats of India for treating inflammation , hepatitis and jaundice for many years and their effectiveness is widely acclaimed among the tribal communities .
AIM OF THE STUDY : To evaluate the mechanisms behind the antioxidant and hepatoprotective potential of Orthosiphon diffusus methanol active fraction ( MAF ) using in vivo ( rat ) and in vitro ( cell culture ) models .
MATERIALS AND METHODS : Neutralization of CCl4-induced hepatotoxicity by MAF was evaluated in rats .
Towards @ @ @ @ @ @ @ markers ( lactate dehydrogenase and alkaline phosphatase ) , antioxidant enzymes in the liver homogenates , and histological examination were performed .
In in vitro studies , mechanisms of neutralization of H2O2-induced toxicity by MAF using MTT , Comet assay and up-regulation of antioxidant enzymes at genetic level ( RT-PCR ) was performed in HepG2 cells .
RESULTS : Rats pre-treated with Orthosiphon diffusus MAF demonstrated significantly reduced levels of serum LDH ( 1.3-fold , p < 0.05 ) and ALP ( 1.6-fold , p < 0.05 ) .
Similarly , multiple dose @ @ @ @ @ @ @ p < 0.05 ) of antioxidant enzymes in the liver homogenates .
Histological analysis revealed complete neutralization of CCl4-induced liver injury by the extract .
The in vitro studies demonstrated that , pre-treatment of MAF effectively prevented H2O2-induced oxidative stress , genotoxicity and significantly enhanced ( ~6-fold , p < 0.01 ) expression of genes for antioxidant enzymes .
CONCLUSIONS : Orthosiphon diffusus MAF demonstrated significant hepatoprotection against CCl4-induced hepatotoxicity by antioxidant mechanisms comparable to silymarin .
H2O2-induced oxidative stress was completely neutralized by MAF through enhanced expression of genes for antioxidant enzymes @ @ @ @ @ @ @ use of Orthosiphon diffusus by folk medicinal practitioners in India .
Further , MAF of Orthosiphon diffusus can serve as a strong candidate for the development of herbal hepatoprotective agents .

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations of Orthosiphon diffusus (Benth.) have been used by folk medicinal practitioners in the Western Ghats of India for treating inflammation, hepatitis and jaundice for many years and their effectiveness is widely acclaimed among the tribal communities.
AIM OF THE STUDY: To evaluate the mechanisms behind the antioxidant and hepatoprotective potential of Orthosiphon diffusus methanol active fraction (MAF) using in vivo (rat) and in vitro (cell culture) models.
MATERIALS AND METHODS: Neutralization of CCl4-induced hepatotoxicity by MAF was evaluated in rats. Towards this, serum levels of hepatic injury markers (lactate dehydrogenase and alkaline phosphatase), antioxidant enzymes in the liver homogenates, and histological examination were performed. In in vitro studies, mechanisms of neutralization of H2O2-induced toxicity by MAF using MTT, Comet assay and up-regulation of antioxidant enzymes at genetic level (RT-PCR) was performed in HepG2 cells.
RESULTS: Rats pre-treated with Orthosiphon diffusus MAF demonstrated significantly reduced levels of serum LDH (1.3-fold, p<0.05) and ALP (1.6-fold, p<0.05). Similarly, multiple dose MAF administration demonstrated significantly enhanced levels (p<0.05) of antioxidant enzymes in the liver homogenates. Histological analysis revealed complete neutralization of CCl4-induced liver injury by the extract. The in vitro studies demonstrated that, pre-treatment of MAF effectively prevented H2O2-induced oxidative stress, genotoxicity and significantly enhanced (~6-fold, p<0.01) expression of genes for antioxidant enzymes.
CONCLUSIONS: Orthosiphon diffusus MAF demonstrated significant hepatoprotection against CCl4-induced hepatotoxicity by antioxidant mechanisms comparable to silymarin. H2O2-induced oxidative stress was completely neutralized by MAF through enhanced expression of genes for antioxidant enzymes. Therefore, this study validates the use of Orthosiphon diffusus by folk medicinal practitioners in India. Further, MAF of Orthosiphon diffusus can serve as a strong candidate for the development of herbal hepatoprotective agents.


greenmedinfo--2020-12-21--Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon

Urinary metabolic profiling of cisplatin nephrotoxicity and nephroprotective effects of Orthosiphon stamineus leaves.

Orthosiphon stamineus ( OS ) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders .
This study employedH NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities .
Aqueous ( OSAE ) and 50 % aqueous ethanolic ( OSFE ) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose .
TheH NMR profile of the urine samples collected on day 5 @ @ @ @ @ @ @ pattern recognition techniques , whereby 19 marker metabolites suggestive in the involvement of TCA cycle , disturbed energy metabolism , altered gut microflora and BCAA metabolism pathways were identified .
It was observed that OSFE caused significant changes ( p < 0.05 ) in the levels of 8 markers namely leucine , acetate , hippurate , lysine , valine , 2-oxoglutarate , 3-HBT and acetoacetate resulting in a moderate ameliorative effect , however , it did not completely protect from nephrotoxicity .
OSAE did not demonstrate significant down regulatory effects on any markers @ @ @ @ @ @ @ nephrotoxicity by inducing significant increase in glucose , glycine , creatinine , citrate , TMAO , acetate and creatine levels .
A Principal Component Analysis ( PCA ) of theH NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid , chlorogenic acid , protocatechuic acid and orthosiphol , among others .
Whereas , OSAE was characterized by higher concentrations of acetate , lactate , succinic acid , valine and phosphatidylcholine .
This research denotes the first comprehensive analysis to identify the effects of @ @ @ @ @ @

Orthosiphon stamineus (OS) is a popular medicinal herb used in traditional Chinese medicine as a diuretic agent and for renal system disorders. This study employedH NMR based metabolomics approach to investigate the possible protective activity of OS in cisplatin induced nephrotoxicity owing to its diuretic and antioxidant activities. Aqueous (OSAE) and 50% aqueous ethanolic (OSFE) extracts of OS leaves were orally administered at 400mg/kg BW doses to rats which were then intraperitoneally injected with cisplatin at 5mg/kg BW dose. TheH NMR profile of the urine samples collected on day 5 after cisplatin administration were analyzed by multivariate pattern recognition techniques, whereby 19 marker metabolites suggestive in the involvement of TCA cycle, disturbed energy metabolism, altered gut microflora and BCAA metabolism pathways were identified. It was observed that OSFE caused significant changes (p<0.05) in the levels of 8 markers namely leucine, acetate, hippurate, lysine, valine, 2-oxoglutarate, 3-HBT and acetoacetate resulting in a moderate ameliorative effect, however, it did not completely protect from nephrotoxicity. OSAE did not demonstrate significant down regulatory effects on any markers, albeit, it potentiated the cisplatin nephrotoxicity by inducing significant increase in glucose, glycine, creatinine, citrate, TMAO, acetate and creatine levels. A Principal Component Analysis (PCA) of theH NMR spectra of OS extracts identified that OSFE had higher concentrations of the secondary metabolites such as caffeic acid, chlorogenic acid, protocatechuic acid and orthosiphol, among others. Whereas, OSAE was characterized by higher concentrations of acetate, lactate, succinic acid, valine and phosphatidylcholine. This research denotes the first comprehensive analysis to identify the effects of OS extracts on cisplatin nephrotoxicity.


greenmedinfo--2020-12-21--Orthosiphon stamineus standardized extract reverses streptozotocin-induced Alzheimer's disease-like

Orthosiphon stamineus standardized extract reverses streptozotocin-induced Alzheimer's disease-like condition.

Alzheimer 's disease ( AD ) is a chronic neurodegenerative brain disease that is characterized by impairment in cognitive functioning as well as the presence of intraneuronal neurofibrillary tangles ( NFTs ) and extracellular senile plaques .
There is a growing interest in the potential of phytochemicals to improve memory , learning , and general cognitive abilities .
The Malaysian herbis a traditional remedy that possesses anti-inflammatory , anti-oxidant , and free-radical scavenging abilities , all of which are known to protect against AD .
Previous studies have reported that intracerebroventricular ( ICV ) administration of streptozotocin ( STZ ) @ @ @ @ @ @ @ in AD .
This experiment thus aimed to explore if an ethanolic leaf extract ofhas the potential to be a novel treatment for AD in a rat model and can reverse the STZ- induced learning and memory dysfunction .
The results of this study indicate thathas the potential to be potentially effective against AD-like condition , as both behavioral models employed in this study was observed to be able to reverse memory impairment .
Treatment with the extract was able to decrease the up-regulated expression levels of amyloid precursor protein ( APP ) @ @ @ @ @ @ @ ) , Nuclear factor kappa-light-chain-enhancer of activated B cells ( NFᴋB ) , glycogen synthase kinase 3 alpha ( GSK3α ) , and glycogen synthase kinase 3 beta ( GSK3β ) genes indicating the extract 's neuroprotective ability .
These research findings suggest that theethanolic extract demonstrated an improved effect on memory , and hence , could serve as a potential therapeutic target for the treatment of neurodegenerative diseases such as AD .

Alzheimer's disease (AD) is a chronic neurodegenerative brain disease that is characterized by impairment in cognitive functioning as well as the presence of intraneuronal neurofibrillary tangles (NFTs) and extracellular senile plaques. There is a growing interest in the potential of phytochemicals to improve memory, learning, and general cognitive abilities. The Malaysian herbis a traditional remedy that possesses anti-inflammatory, anti-oxidant, and free-radical scavenging abilities, all of which are known to protect against AD. Previous studies have reported that intracerebroventricular (ICV) administration of streptozotocin (STZ) mimics a condition similar to that observed in AD. This experiment thus aimed to explore if an ethanolic leaf extract ofhas the potential to be a novel treatment for AD in a rat model and can reverse the STZ- induced learning and memory dysfunction. The results of this study indicate thathas the potential to be potentially effective against AD-like condition, as both behavioral models employed in this study was observed to be able to reverse memory impairment. Treatment with the extract was able to decrease the up-regulated expression levels of amyloid precursor protein (APP), microtubule associated protein tau (MAPT), Nuclear factor kappa-light-chain-enhancer of activated B cells (NFᴋB), glycogen synthase kinase 3 alpha (GSK3α), and glycogen synthase kinase 3 beta (GSK3β) genes indicating the extract's neuroprotective ability. These research findings suggest that theethanolic extract demonstrated an improved effect on memory, and hence, could serve as a potential therapeutic target for the treatment of neurodegenerative diseases such as AD.


greenmedinfo--2020-12-21--A comparative study of the antioxidant and intestinal protective effects of extracts from different

A comparative study of the antioxidant and intestinal protective effects of extracts from different parts of Java tea.

The aim of this study was to compare the free radical scavenging ability and intestinal epithelial cell protective effects of @ @ @ @ @ extracts ( ORE ) , stem extracts ( OSE ) , and leaf extracts ( @ @ @ @ @ potential of Java tea by-products .
The Java tea extracts were prepared using a standard @ @ @ @ @ activity and intestinal protective effects were tested by HO-induced cell model and high-fat diet-induced mice @ @ @ @ @ results showed that the total phenolic acid and flavonoid content and relative content were different @ @ @ @ @ , and OLE .
ORE had the highest total polyphenol and flavonoid content , the @ @ @ @ @ , and the highest intracellular free radical scavenging rate .
However , the yeast content @ @ @ @ @ than that in the OSE and OLE .
All the Java tea extracts protected mouse @ @ @ @ @ injury .
This study indicates the potential of Java tea extracts as food or feed @ @ @ @ @ from oxidative stress .

The aim of this study was to compare the free radical scavenging ability and intestinal epithelial cell protective effects of Java tea () root extracts (ORE), stem extracts (OSE), and leaf extracts (OLE) to determine the potential of Java tea by-products. The Java tea extracts were prepared using a standard water-ethanol method. The antioxidant activity and intestinal protective effects were tested by HO-induced cell model and high-fat diet-induced mice model, respectively. The results showed that the total phenolic acid and flavonoid content and relative content were different in the ORE, OSE, and OLE. ORE had the highest total polyphenol and flavonoid content, the highest free radical scavenging rate, and the highest intracellular free radical scavenging rate. However, the yeast content in the ORE was lower than that in the OSE and OLE. All the Java tea extracts protected mouse intestine from high-fat diet-induced oxidative injury. This study indicates the potential of Java tea extracts as food or feed additives to protect the intestine from oxidative stress.


greenmedinfo--2020-12-21--Glucose uptake stimulatory and PTP1B inhibitory activities of pimarane diterpenes from Orthosiphon s

Glucose uptake stimulatory and PTP1B inhibitory activities of pimarane diterpenes from Orthosiphon stamineus.

Seven pimarane diterpenes ( - ) were isolated fromBenth .
by assay-guided isolation .
All of the isolates possessed a @ @ @ @ @ amino ) -d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10μM .
@ @ @ @ @ inhibition against protein tyrosine phosphatase 1B with ICvalues ranging from 0.33 to 9.84μM .
In @ @ @ @ @ inhibition types were exposed for the examined potencies , including mixed-competitive ( ) , non-competitives @ @ @ @ @ ( ) , and uncompetitive ( ) .
The results suggested thatand its pimarane diterpenes @ @ @ @ @ via the insulin signaling pathway targeting inhibition of protein tyrosine phosphatase 1B ( PTP1B ) @ @

Seven pimarane diterpenes (-) were isolated fromBenth. by assay-guided isolation. All of the isolates possessed a 2-deoxy-2-((7-nitro-2,1,3-benzoxadiazol-4-yl)amino)-d-glucose uptake effect in 3T3-L1 adipocytes at concentrations of 5 and 10μM. Most of them showed potent inhibition against protein tyrosine phosphatase 1B with ICvalues ranging from 0.33 to 9.84μM. In the kinetic study, all inhibition types were exposed for the examined potencies, including mixed-competitive (), non-competitives (and), competitive (), and uncompetitive (). The results suggested thatand its pimarane diterpenes might exert the hypoglycemic effect via the insulin signaling pathway targeting inhibition of protein tyrosine phosphatase 1B (PTP1B) activity.


greenmedinfo--2020-12-21--Flavonoids-rich Orthosiphon stamineus extract as new candidate for angiotensin I-converting enzyme i

Flavonoids-rich Orthosiphon stamineus extract as new candidate for angiotensin I-converting enzyme inhibition.

This study aims to evaluate the in vitro angiotensin-converting enzyme ( ACE ) inhibition activity of different extracts of ( OS ) leaves and their main flavonoids , namely rosmarinic acid ( RA ) , sinensetin ( SIN ) , eupatorin ( EUP ) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone ( TMF ) .
Furthermore , to identify possible mechanisms of action based on structure-activity relationships and molecular docking .
The in vitro ACE inhibition activity relied on determining hippuric acid ( HA ) formation from ACE-specific substrate ( hippuryl-histidyl-leucine ( HHL ) ) by the action of ACE enzyme .
A High Performance @ @ @ @ @ @ @ was developed and validated for measurement the concentration of produced HA .
The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent .
Furthermore , molecular docking study was performed by : BioSolveIT 's LeadIT program .
OS ethanolic extract ( OS-E ) exhibited highest inhibition and lowest ICvalue ( 45.77± 1.17 µg/mL ) against ACE compared to the other extracts .
Among the tested reference compounds , EUP with IC15.35± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn ( II ) ( 56.03 @ @ @ @ @ @ @ RA , TMF and SIN .
Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with aminoacids in the active site .
In this study , we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE .
Moreover , we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme .
It was also revealed that OS extract @ @ @ @ @ @ @ RA , TMF , SIN and EUP .
As such , application of OS extract is useful as inhibitors of ACE .

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of(OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure-activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by: BioSolveIT's LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest ICvalue (45.77± 1.17 µg/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC15.35± 4.49 µg/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% ± 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with aminoacids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE.


greenmedinfo--2020-12-21--Antiobesity and lipid lowering effects of Orthosiphon stamineus in high-fat diet-induced obesity.

This website is for information purposes only .
By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

The present study investigated the antiobesity and lipid lowering effects of an ethanolic extract of leaves obtained from(200 and 400 mg/kg) and its major compound (rosmarinic acid, 10 mg/kg) in obese mice (C57BL/6) induced by a high-fat diet. Continuous supplementation withextract (200 and 400 mg/kg) for 8 weeks significantly decreased body weight gain (p < 0.05). However, supplementation with rosmarinic acid, a constituent in the extract, produced only a slight reduction in body weight gain compared to the high-fat diet control group. Food intake between the treatment and the high-fat diet groups was similar, which suggested that the plant extractdid not suppress food intake. Further, body weight reduction of the treatment groups was not due to a decreased reduction in energy intake. Compared to the high-fat diet-fed group, serum triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels were significantly reduced in the treated groups, while high-density lipoprotein cholesterol levels were not significantly altered. Accumulation of hepatic lipid droplets induced by a high-fat diet was markedly inhibited byextract. In addition,significantly diminished liver malondialdehyde production, and significantly elevated the activities of hepatic superoxidase dismutase. The present study showed that an ethanolic extract prepared from the leaves ofcan significantly reduce a gain in body weight, enhance antioxidant activity, and possess hypolipidemic and antiobesity effects, thereby protecting against the adverse effects of high-fat diet-induced obesity.


greenmedinfo--2020-12-21--Technocracy and the Great Reset

Technocracy and the Great Reset

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
© Copyright 2008-2023 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.


greenmedinfo--2020-12-21--Orthosiphon stamineus tea modulates arthritis pathogenesis.

BACKGROUND : Orthosiphon stamineus is used traditionally to treat gout , arthritis , and inflammatory related conditions .
The in vitro anti-inflammatory effects of the plant have been scientifically investigated .
The goal of the present study was to evaluate the potential of the 50 % ethanol extract of O. stamineus ( EOS ) to treat rheumatoid arthritis .
METHODS : Anti-arthritic activity was assessed using the in vitro heat denaturation test and the ( FCA ) -induced arthritis model .
Efficacy was assessed by measurements of paw edema and granulation , X-ray radiography , fluorescence molecular tomography ( FMT @ @ @ @ @ @ @ of ( TNF-α ) , interleukin-1 ( IL-1 ) , and ( COX-1 and COX-2 ) were analyzed in vitro in lipopolysaccharide ( LPS ) -stimulated human macrophage ( U937 ) .
TNF-α and IL-1 levels in the serum samples of arthritic rats were also measured using an ELISA kit .
RESULTS : Treatment with EOS resulted in dose-dependent inhibition of paw edema in acute and chronic models of inflammation .
It also inhibited significantly the production of TNF-α , IL-1 COX-1 , and COX-2 in the LPS-stimulated U937 macrophages .
EOS significantly @ @ @ @ @ @ @ the serum levels of TNF-α and IL-1 .
X-rays of the synovial joint of the hind leg showed considerable improvement in joint integrity and recovery of tibia-talus bones fromdegeneration and osteoporotic lesions .
Histology of proximal interphalangeal joints of EOS-treated animals showed obvious protection of cartilage and soft tissue .
Finally , FMT analysis strongly supported the anti-arthritic effect of EOS .
EOS had high phenolic and total flavonoid content as well as strong antioxidant activity .
CONCLUSIONS : Results illustrated that the anti-arthritic properties of O. stamineus could be beneficial for prevention @ @ @ @ @ @ @ chronic inflammatory disorders .
Illustration of the Anti- arthritis efficacy of Orthosiphon Stamineus standardized extract .

BACKGROUND: Orthosiphon stamineus is used traditionally to treat gout, arthritis, and inflammatory related conditions. The in vitro anti-inflammatory effects of the plant have been scientifically investigated. The goal of the present study was to evaluate the potential of the 50% ethanol extract of O. stamineus (EOS) to treat rheumatoid arthritis.
METHODS: Anti-arthritic activity was assessed using the in vitro heat denaturation test and the (FCA)-induced arthritis model. Efficacy was assessed by measurements of paw edema and granulation, X-ray radiography, fluorescence molecular tomography (FMT), and histological evaluation. Levels of (TNF-α), interleukin-1 (IL-1), and (COX-1 and COX-2) were analyzed in vitro in lipopolysaccharide (LPS)-stimulated human macrophage (U937). TNF-α and IL-1 levels in the serum samples of arthritic rats were also measured using an ELISA kit.
RESULTS: Treatment with EOS resulted in dose-dependent inhibition of paw edema in acute and chronic models of inflammation. It also inhibited significantly the production of TNF-α, IL-1 COX-1, and COX-2 in the LPS-stimulated U937 macrophages. EOS significantly suppressed FCA-induced paw edema as well as the serum levels of TNF-α and IL-1. X-rays of the synovial joint of the hind leg showed considerable improvement in joint integrity and recovery of tibia-talus bones fromdegeneration and osteoporotic lesions. Histology of proximal interphalangeal joints of EOS-treated animals showed obvious protection of cartilage and soft tissue. Finally, FMT analysis strongly supported the anti-arthritic effect of EOS. EOS had high phenolic and total flavonoid content as well as strong antioxidant activity.
CONCLUSIONS: Results illustrated that the anti-arthritic properties of O. stamineus could be beneficial for prevention and management of rheumatoid arthritis and other chronic inflammatory disorders. Illustration of the Anti- arthritis efficacy of Orthosiphon Stamineus standardized extract.


greenmedinfo--2020-12-21--Toxicological studies of Orthosiphon stamineus standardized ethanol extract in combination with gemc

Toxicological studies of Orthosiphon stamineus standardized ethanol extract in combination with gemcitabine.

Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment .
@ @ @ @ @ anticancer drug has reduced efficacy due to acquired resistance .
The current study evaluates the @ @ @ @ @ and its marker compound ( rosmarinic acid ) in combination with gemcitabine .
( 200 @ @ @ @ @ rosmarinic acid ( 32 mg/kg/day ) were administered orally and gemcitabine ( 10 mg/kg/3 days @ @ @ @ @ in combination treatment for fourteen days .
Parameters including blood serum biochemistry , hematology , @ @ @ @ @ lethality , and histopathological analysis of liver , kidney , and spleen tissues were studied @ @ @ @ @ nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude @ @ @ @ @ group .
Toxicological data obtained from this study will help to select the best doses @ @ @ @ @ pancreatic xenograft tumor studies .

Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of() and its marker compound (rosmarinic acid) in combination with gemcitabine.(200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.


greenmedinfo--2020-12-21--Polymethoxylated flavones from Orthosiphon stamineus leaves as antiadhesive compounds against uropat

Polymethoxylated flavones from Orthosiphon stamineus leaves as antiadhesive compounds against uropathogenic E. coli.

Aqueous and acetone extracts of O. stamineus leaves reduce the adhesion of uropathogenic E. coli ( UPEC , strain UTI89 ) to T24 bladder cells significantly ( IC~ 524 mg/mL , resp .
40 μg/mL ) .
The acteonic extract had no cytotoxic effects against UPEC in concentrations that inhibited the bacterial adhesion .
The extract significantly reduced the gene expression of fimH , fimC , fimD , csgA and focG , which are strongly involved in the formation of bacterial adhesins .
The antiadhesive effect was due to the presence of polymethoxylated flavones , enriched in the acetonic extract @ @ @ @ @ @ @ fast centrifugal partition chromatography , followed by preparative HPLC .
Eupatorin , ladanein , salvigenin , sinensetin , 5,6,7,4'-tetramethoxyflavone and 5-hydroxy-6,7,3',4'-tetramethoxyflavone were identified as the main polymethoxylated flavones .
With the exception of eupatorin , all of these flavones reduced the bacterial adhesion in a concentration depending manner , indicating that B-ring hydroxylation and methoxylation seems to have a major impact on the antiadhesive activity .
In addition , this was confirmed by investigation of the flavones chrysoeriol and diosmetin , which had only very weak antiadhesive activity .
From these data , @ @ @ @ @ @ @ a pronounced antiadhesive activity against UPEC , based on a variety of polymethoxylated flavones .

Aqueous and acetone extracts of O. stamineus leaves reduce the adhesion of uropathogenic E. coli (UPEC, strain UTI89) to T24 bladder cells significantly (IC~ 524 mg/mL, resp. 40 μg/mL). The acteonic extract had no cytotoxic effects against UPEC in concentrations that inhibited the bacterial adhesion. The extract significantly reduced the gene expression of fimH, fimC, fimD, csgA and focG, which are strongly involved in the formation of bacterial adhesins. The antiadhesive effect was due to the presence of polymethoxylated flavones, enriched in the acetonic extract. Five flavones have been isolated by fast centrifugal partition chromatography, followed by preparative HPLC. Eupatorin, ladanein, salvigenin, sinensetin, 5,6,7,4'-tetramethoxyflavone and 5-hydroxy-6,7,3',4'-tetramethoxyflavone were identified as the main polymethoxylated flavones. With the exception of eupatorin, all of these flavones reduced the bacterial adhesion in a concentration depending manner, indicating that B-ring hydroxylation and methoxylation seems to have a major impact on the antiadhesive activity. In addition, this was confirmed by investigation of the flavones chrysoeriol and diosmetin, which had only very weak antiadhesive activity. From these data, Orthosiphon extracts can be assessed to have a pronounced antiadhesive activity against UPEC, based on a variety of polymethoxylated flavones.


greenmedinfo--2020-12-21--50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mi

50% Ethanol extract of Orthosiphon stamineus modulates genotoxicity and clastogenicity induced by mitomycin C.

Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens .
Orthosiphon stamineus ( O.s ) also known as Cat whiskers .
The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect .
The study aimed to evaluate the effects of different doses ( 250 , 500 and 1000 mg kg ) of 50 % ethanol extract of O.s ( Et .
O.s ) on micro-nucleated polychromatic erythrocytes ( MNPCE ) , Polychromatic to normachromatic erythrocytes ratio ( PCE/NCE ) , Mitotic index ( @ @ @ @ @ @ @ CA ) in Bab/c mice .
Moreover , these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of ( Et .
O.s ) against mitomycin c ( MMC ) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells .
MMC ( 4 mg kg ) was injected intraperitoneally ( i.p . )
to the mice before and after treatment with three different doses of ( Et .
O.s ) .
The results indicated that the extract at different doses did not show significant ( p ≥ @ @ @ @ @ @ @ , ( PCE/NCE ) ratios , and ( CA ) values .
The higher doses sowed high ( MI ) values compared with untreated control group .
MMC showed significant increase ( p ≤ 0.001 ) in ( MNPCE ) , ( CA ) and reduce ( PCE/NCE ) and ( MI ) values compared with untreated control group .
Treatment with ( Et .
O.s ) at different doses before and after MMC injection showed to modulate MNPCE , PCE/NCE ratios , CA and MI values in mice bone marrow cells suggesting @ @ @ @ @ @ @

Herbal products contain a variety of compounds which may be useful in protecting against cellular damage caused by mutagens. Orthosiphon stamineus (O.s) also known as Cat whiskers. The herb has been shown anti-oxidative properties and can modulate key cellular proteins that have cytoprotective effect. The study aimed to evaluate the effects of different doses (250, 500 and 1000 mg kg) of 50% ethanol extract of O.s (Et. O.s) on micro-nucleated polychromatic erythrocytes (MNPCE), Polychromatic to normachromatic erythrocytes ratio (PCE/NCE), Mitotic index (MI), and Chromosomal aberration (CA) in Bab/c mice. Moreover, these parameters were used to evaluate the anti-genotoxic and clastogenic potencies of (Et. O.s) against mitomycin c (MMC) that interact with biological molecules and induce genotoxic and clastogenic disorders in non-tumor cells. MMC (4 mg kg) was injected intraperitoneally (i.p.) to the mice before and after treatment with three different doses of (Et. O.s). The results indicated that the extract at different doses did not show significant (p ≥ 0.05) differences in (MNPCE), (PCE/NCE) ratios, and (CA) values. The higher doses sowed high (MI) values compared with untreated control group. MMC showed significant increase (p ≤ 0.001) in (MNPCE), (CA) and reduce (PCE/NCE) and (MI) values compared with untreated control group. Treatment with (Et. O.s) at different doses before and after MMC injection showed to modulate MNPCE, PCE/NCE ratios, CA and MI values in mice bone marrow cells suggesting genoprotective potential of this plant extract.


greenmedinfo--2020-12-23--FDA Investigates Allergic Reactions to Pfizer COVID Vaccine After More Healthcare Workers Hospitaliz

FDA Investigates Allergic Reactions to Pfizer COVID Vaccine After More Healthcare Workers Hospitalized


greenmedinfo--2020-12-22--Crocin induces autophagic cell death and inhibits cell invasion of cervical cancer SiHa cells throug

Crocin induces autophagic cell death and inhibits cell invasion of cervical cancer SiHa cells through activation of PI3K/AKT.

Background : Cervical cancer is a prevalent tumor mainly induced by Human Papilloma Virus ( HPV ) .
Autophagy was inactivated with HPV to promote cancer progression .
Here we explored the effects of crocin on cervical cancer cells , mainly on autophagy and apoptosis .
Methods : SiHa cells were treated with crocin , and proliferation , metastases , apoptosis and autophagy were measured using a CCK-8 assay , transwell migration assay , flow cytometry and immunofluorescence .
Protein levels were measured using western blotting .
The antitumor effects of crocin were validated in female BALB/c nude mice injected @ @ @ @ @ @ @ result showed that 2 , 4 , 8 and 16 mM of crocin significantly reduced the viability of SiHa cells within 24 h. Subsequently , 0 , 1 , 2 and 4 mM crocin concentrations were used in later experiments .
Treatment with crocin reduced invasive cells , while increasing autophagic and apoptotic cells dose-dependently .
The enhanced apoptosis and autophagy were partly validated by an increase in cleaved caspase-3/caspase-3 , cleaved caspase-9/caspase9 , LC3B II/I , Beclin1 and ATG7 .
AMPK and mTOR were inactivated with crocin treatment , while PI3K was @ @ @ @ @ @ @ might promote autophagy and apoptosis by inactivating AMPK and mTOR signaling .
Tumor progression was inhibited in mice treated with 50 mg/kg/d of crocin , which was demonstrated by smaller tumor volumes , less VEGF expression , more intense caspase-3 staining and increased LC3B II/I in the tumor tissues .
Conclusions : Crocin inhibited the progression of cervical cancerand , possibly through inactivation of AMPK and mTOR , inhibition of proliferation and invasion , and promotion of autophagy and apoptosis .
These results support the potential therapeutic value of crocin in treating cervical @ @

Background: Cervical cancer is a prevalent tumor mainly induced by Human Papilloma Virus (HPV). Autophagy was inactivated with HPV to promote cancer progression. Here we explored the effects of crocin on cervical cancer cells, mainly on autophagy and apoptosis.
Methods: SiHa cells were treated with crocin, and proliferation, metastases, apoptosis and autophagy were measured using a CCK-8 assay, transwell migration assay, flow cytometry and immunofluorescence. Protein levels were measured using western blotting. The antitumor effects of crocin were validated in female BALB/c nude mice injected with SiHa cells.
Results: The result showed that 2, 4, 8 and 16 mM of crocin significantly reduced the viability of SiHa cells within 24 h. Subsequently, 0, 1, 2 and 4 mM crocin concentrations were used in later experiments. Treatment with crocin reduced invasive cells, while increasing autophagic and apoptotic cells dose-dependently. The enhanced apoptosis and autophagy were partly validated by an increase in cleaved caspase-3/caspase-3, cleaved caspase-9/caspase9, LC3B II/I, Beclin1 and ATG7. AMPK and mTOR were inactivated with crocin treatment, while PI3K was activated. These results indicated that crocin might promote autophagy and apoptosis by inactivating AMPK and mTOR signaling. Tumor progression was inhibited in mice treated with 50 mg/kg/d of crocin, which was demonstrated by smaller tumor volumes, less VEGF expression, more intense caspase-3 staining and increased LC3B II/I in the tumor tissues.
Conclusions: Crocin inhibited the progression of cervical cancerand, possibly through inactivation of AMPK and mTOR, inhibition of proliferation and invasion, and promotion of autophagy and apoptosis. These results support the potential therapeutic value of crocin in treating cervical cancer.


greenmedinfo--2020-12-22--Crocin restrained the activation of hepatic stellate cells through the lnc-LFAR1/MTF-1/GDNF axis, th

Crocin restrained the activation of hepatic stellate cells through the lnc-LFAR1/MTF-1/GDNF axis, thereby ameliorating liver fibrosis.

Crocin is the main monomer of saffron , which is a momentous component of traditional Chinese medicine Lang Qing A Ta .
Here , we tried to probe into the role of crocin in liver fibrosis .
Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues .
After hepatic stellate cells ( HSCs ) were isolated from liver tissues , lnc-LFAR1 , MTF-1 , GDNF , andα-SMA expressions were detected by qRT-PCR and western blot .
Immunohistochemistry and immunofluorescence were used to detect α-SMA expression .
Chromatin immunoprecipitation was used to analyze the @ @ @ @ @ @ @ .
Moreover , the dual-luciferase reporter gene , RNA pull-down , and RNA immunoprecipitation were used to clarify the interaction between MTF-1 and GDNF , lnc-LFAR1 and MTF-1 .
The degree of liver fibrosis was more severe in the mice from the liver fibrosis model , while the liver fibrosis was alleviated by the injection of crocin .
lnc-LFAR1 , GDNF , and α-SMA were up-regulated , and MTF-1 was down-regulated in liver fibrosis tissues and cells , while these trends were reversed after the injection of crocin .
Besides , lnc-LFAR1 negatively @ @ @ @ @ @ @ GDNF and α-SMA expressions , and MTF-1 was enriched in the promoter regionof GDNF .
Furthermore , the cellular direct interactions between MTF-1 and GDNF , lnc-LFAR1 and MTF-1 were verified.experiments confirmed the relief of crocin on liver fibrosis .
Our research expounded that crocin restrained the activation of HSCs through the lnc-LFAR1/MTF-1/GDNF axis , thereby ameliorating liver fibrosis .

Crocin is the main monomer of saffron, which is a momentous component of traditional Chinese medicine Lang Qing A Ta. Here, we tried to probe into the role of crocin in liver fibrosis. Hematoxylin-eosin staining and Sirius Red staining were used to observe the pathological changes of liver tissues. After hepatic stellate cells (HSCs) were isolated from liver tissues, lnc-LFAR1, MTF-1, GDNF, andα-SMA expressions were detected by qRT-PCR and western blot. Immunohistochemistry and immunofluorescence were used to detect α-SMA expression. Chromatin immunoprecipitation was used to analyze the binding of MTF-1 to the GDNF promoter. Moreover, the dual-luciferase reporter gene, RNA pull-down, and RNA immunoprecipitation were used to clarify the interaction between MTF-1 and GDNF, lnc-LFAR1 and MTF-1. The degree of liver fibrosis was more severe in the mice from the liver fibrosis model, while the liver fibrosis was alleviated by the injection of crocin. lnc-LFAR1, GDNF, and α-SMA were up-regulated, and MTF-1 was down-regulated in liver fibrosis tissues and cells, while these trends were reversed after the injection of crocin. Besides, lnc-LFAR1 negatively regulated MTF-1 expression, and positively regulated GDNF and α-SMA expressions, and MTF-1 was enriched in the promoter regionof GDNF. Furthermore, the cellular direct interactions between MTF-1 and GDNF, lnc-LFAR1 and MTF-1 were verified.experiments confirmed the relief of crocin on liver fibrosis. Our research expounded that crocin restrained the activation of HSCs through the lnc-LFAR1/MTF-1/GDNF axis, thereby ameliorating liver fibrosis.


greenmedinfo--2020-12-22--Crocin significantly decreased chronic constriction injury-induced neuropathic pain.

Objective : Crocin as an important constituent of saffron has antineuropathic pain properties ; however , the exact mechanism of this effect is not known .
The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors .
Materials and Methods : In the present project , 36 male Wistar rats ( 200 ± 20 g ) were used .
Animals randomly divided into six groups ( sham , neuropathy , neuropathy + crocin , neuropathy + atropine 0.5 mg/kg , neuropathy + atropine 1 mg/kg , and neuropathy + atropine 1 mg/kg @ @ @ @ @ @ @ by the chronic constriction injury ( CCI ) method on the sciatic nerve .
Crocin and atropine was administered intraperitoneally during 14 days following the 14day after surgery .
Pain response was detected every three days , two hours after each injection and 3 days following last injection .
Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device , respectively .
Results : CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus ( < 0.01 and < 0.05 , respectively ) .
Crocin @ @ @ @ @ @ @ hyperalgesia induced by CCI ( < 0.05 ) .
Atropine pretreatment significantly blocked the hypoalgesic effect of crocin ( < 0.05 in mechanical allodynia and < 0.01 in thermal hyperalgesia ) .
Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery .
Conclusion : Crocin significantly decreased CCI-induced neuropathic pain .
The hypoalgesic effect of crocin was blocked by atropine pretreatment , which indicates an important role for muscarinic receptors in the effect of crocin .

Objective: Crocin as an important constituent of saffron has antineuropathic pain properties; however, the exact mechanism of this effect is not known. The aim of this study was whether the hypoalgesic effect of crocin can be exerted through muscarinic receptors.
Materials and Methods: In the present project, 36 male Wistar rats (200 ± 20 g) were used. Animals randomly divided into six groups (sham, neuropathy, neuropathy + crocin, neuropathy + atropine 0.5 mg/kg, neuropathy + atropine 1 mg/kg, and neuropathy + atropine 1 mg/kg + crocin). Neuropathy was induced by the chronic constriction injury(CCI) method on the sciatic nerve. Crocin and atropine was administered intraperitoneally during 14 days following the 14day after surgery. Pain response was detected every three days, two hours after each injection and 3 days following last injection. Mechanical allodynia and thermal hyperalgesia were detected using the Von Frey filaments and plantar test device, respectively.
Results: CCI significantly reduced the paw withdrawal response to mechanical and thermal stimulus (<0.01 and<0.05, respectively). Crocin therapy significantly reduced mechanical allodynia and thermal hyperalgesia induced by CCI (<0.05). Atropine pretreatment significantly blocked the hypoalgesic effect of crocin (<0.05 in mechanical allodynia and<0.01 in thermal hyperalgesia). Fourteen days administration of atropine alone at a dose of 0.5 mg/kg but not 1 mg/kg significantly reduced CCI-induced mechanical allodynia at day 30 after surgery.
Conclusion: Crocin significantly decreased CCI-induced neuropathic pain. The hypoalgesic effect of crocin was blocked by atropine pretreatment, which indicates an important role for muscarinic receptors in the effect of crocin.


greenmedinfo--2020-12-22--Crocetin alleviates inflammation in MPTP-induced Parkinson's disease models.

Parkinson 's disease ( PD ) is the second most common neurodegenerative disease .
Crocetin , derived from saffron , @ @ @ @ @ such as anti-inflammatory , antioxidant , antifatigue , and anticancer effects .
However , the @ @ @ @ @ remains unclear .
In this study , we designed experiments to investigate the effect of @ @ @ @ @ and the underlying mechanisms .
Our results showed that crocetin treatment attenuates MPTP-induced motor deficits @ @ @ @ @ Bothandexperiments demonstrated that crocetin treatment decreased the expression of inflammatory associated genes and inflammatory cytokines @ @ @ @ @ protected mitochondrial functions against MPP+ induced damage by regulating the mPTP ( ) viability in @ @ @ @ @ ) and Cyp D ( ) dependent manner .
Therefore , our results demonstrate that @ @ @ @ @ Parkinson 's disease .

Parkinson's disease (PD) is the second most common neurodegenerative disease. Crocetin, derived from saffron, exerts multiple pharmacological properties, such as anti-inflammatory, antioxidant, antifatigue, and anticancer effects. However, the effect of crocetin on PD remains unclear. In this study, we designed experiments to investigate the effect of crocetin against MPTP-induced PD models and the underlying mechanisms. Our results showed that crocetin treatment attenuates MPTP-induced motor deficits and protects dopaminergic neurons. Bothandexperiments demonstrated that crocetin treatment decreased the expression of inflammatory associated genes and inflammatory cytokines. Furthermore, crocetin treatment protected mitochondrial functions against MPP+ induced damage by regulating the mPTP () viability in the interaction of ANT () and Cyp D () dependent manner. Therefore, our results demonstrate that crocetin has therapeutic potential in Parkinson's disease.


greenmedinfo--2020-12-22--Central H 2 histaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinocic

Central H 2 histaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain.

Previous findings have shown that saffron ( L. ) extract and its active constituents produce antinociceptive effects in the rat models of orofacial pain .
In the present study , the central Hhistaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain in rats was evaluated .
The guide cannula was implanted into the fourth ventricle in ketamine-xylazine anesthetized rats .
Subcutaneous injection of a diluted formalin solution ( 1.50 % ; 50.00µL ) into a vibrissae pad was used as a model of orofacial pain .
Face rubbing behavior durations were recorded at 3 min blocks @ @ @ @ @ @ @ biphasic pain response ( first phase : 0-3 min and second phase : 15-33 min ) .
Intra-fourth ventricle injections of crocetin ( 5.00 and 10.00 μgμL ) suppressed , whereas yohimbine ( 10.00μg μL ) and naloxone ( 10.00μg μL ) increased the intensity of both phases of pain .
Crocetin-induced antinociception was not prevented by central pretreatment with naloxone .
However , the antinociceptive effect of crocetin ( 5.00μg μL ) was inhibited by prior administration of famotidine ( 10.00μg μL ) and yohimbine ( 10.00μg μL ) .
Our study @ @ @ @ @ @ @ cerebral fourth ventricle attenuated formalin-induced orofacial pain in rats .
Central Hhistaminergic and alpha-2 adrenergic receptors , but not opioid receptors , might be involved in crocetin-induced antinociception .

Previous findings have shown that saffron (L.) extract and its active constituents produce antinociceptive effects in the rat models of orofacial pain. In the present study, the central Hhistaminergic and alpha-2 adrenergic receptors involvement in crocetin-induced antinociception in orofacial formalin pain in rats was evaluated. The guide cannula was implanted into the fourth ventricle in ketamine-xylazine anesthetized rats. Subcutaneous injection of a diluted formalin solution (1.50%; 50.00µL) into a vibrissae pad was used as a model of orofacial pain. Face rubbing behavior durations were recorded at 3 min blocks for 45 min. Formalin produced a biphasic pain response (first phase: 0-3 min and second phase: 15-33 min). Intra-fourth ventricle injections of crocetin (5.00 and 10.00 μgμL) suppressed, whereas yohimbine (10.00μg μL) and naloxone (10.00μg μL) increased the intensity of both phases of pain. Crocetin-induced antinociception was not prevented by central pretreatment with naloxone. However, the antinociceptive effect of crocetin (5.00μg μL) was inhibited by prior administration of famotidine (10.00μg μL) and yohimbine (10.00μg μL). Our study showed that injection of crocetin into the cerebral fourth ventricle attenuated formalin-induced orofacial pain in rats. Central Hhistaminergic and alpha-2 adrenergic receptors, but not opioid receptors, might be involved in crocetin-induced antinociception.


greenmedinfo--2020-12-22--Ameliorative effects and mechanism of crocetin in arsenic trioxide‑induced cardiotoxicity.

Arsenic trioxide ( ATO ) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s , but its applicability has been limited by its cardiotoxic effects .
Therefore , the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin ( CRT ) , the critical ingredient of saffron .
Sprague‑Dawley rats were then randomly divided into four groups ( n=10/group ) : i ) Control group ; ii ) ATO group , iii ) CRT‑low ( 20 mg/kg ) @ @ @ @ @ @ @ 40 mg/kg ) group .
Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9 % sodium chloride solution , and CRT groups were administered with either 20 and 40 mg/kg CRT .
Following 6 h , all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days .
Cardiotoxicity was indicated by changes in electrocardiographic ( ECG ) patterns , morphology and marker enzymes .
Histomorphological changes in the heart tissue were observed by pathological staining .
The levels of superoxide dismutase @ @ @ @ @ @ @ in the serum were analyzed using colometric commercial assay kits , and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium .
The expression levels of inflammatory factors and activities of apoptosis‑related proteins were analyzed using immunohistochemistry .
The protein expression levels of silent information regulator of transcription 1 were measured using western blotting .
Cardiotoxicity was induced in male Sprague‑Dawley rats with ATO ( 5 mg/kg ) .
CRT ( 20 and 40 mg/kg ) and ATO were co‑administered to evaluate possible cardioprotective effects @ @ @ @ @ @ @ and J‑point elevation induced by ATO in rats .
Histologicalchanges were evaluated via hematoxylin and eosin staining .
CRT decreased the levels of creatine kinase and lactate dehydrogenase , increased the activities of superoxide dismutase , glutathione‑peroxidase and catalase , and decreased the levels of malondialdehyde and reactive oxygen species .
Moreover , CRT downregulated the expression levels of the pro‑inflammatory factors IL‑1 , TNF‑α , IL‑6 , Bax and p65 , as well as increased the expression of Bcl‑2 .
It was also identified that CRT enhanced silent information regulator of transcription @ @ @ @ @ @ @ present study demonstrated that CRT treatment effectively ameliorated ATO‑induced cardiotoxicity .
The protective effects of CRT can be attributed to the inhibition of oxidative stress , inflammation and apoptosis .
Therefore , CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment , and additional clinical applications are possible , but warrant further investigation .

Arsenic trioxide (ATO) is commonly used to treat patients with acute promyelocytic leukemia since it was authorized by the U.S. Food and Drug Administration in the 1970s, but its applicability has been limited by its cardiotoxic effects. Therefore, the aim of the present study was to investigate the cardioprotective effects and underlying mechanism of crocetin (CRT), the critical ingredient of saffron. Sprague‑Dawley rats were then randomly divided into four groups (n=10/group): i) Control group; ii) ATO group, iii) CRT‑low (20 mg/kg) group; and iv) CRT‑high (40 mg/kg) group. Rats in the Control and ATO groups were intraperitoneally injected with equal volumes of 0.9% sodium chloride solution, and CRT groups were administered with either 20 and 40 mg/kg CRT. Following 6 h, all groups except the Control group were intraperitoneally injected with 5 mg/kg ATO over 10 days. Cardiotoxicity was indicated by changes in electrocardiographic (ECG) patterns, morphology and marker enzymes. Histomorphological changes in the heart tissue were observed by pathological staining. The levels of superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase in the serum were analyzed using colometric commercial assay kits, and the levels of reactive oxygen species in the heart tissue were detected using the fluorescent probe dihydroethidium. The expression levels of inflammatory factors and activities of apoptosis‑related proteins were analyzed using immunohistochemistry. The protein expression levels of silent information regulator of transcription 1 were measured using western blotting. Cardiotoxicity was induced in male Sprague‑Dawley rats with ATO (5 mg/kg). CRT (20 and 40 mg/kg) and ATO were co‑administered to evaluate possible cardioprotective effects. CRT significantly reduced the heart rate and J‑point elevation induced by ATO in rats. Histologicalchanges were evaluated via hematoxylin and eosin staining. CRT decreased the levels of creatine kinase and lactate dehydrogenase, increased the activities of superoxide dismutase, glutathione‑peroxidase and catalase, and decreased the levels of malondialdehyde and reactive oxygen species. Moreover, CRT downregulated the expression levels of the pro‑inflammatory factors IL‑1, TNF‑α, IL‑6, Bax and p65, as well as increased the expression of Bcl‑2. It was also identified that CRT enhanced silent information regulator of transcription 1 protein expression. Thus, the present study demonstrated that CRT treatment effectively ameliorated ATO‑induced cardiotoxicity. The protective effects of CRT can be attributed to the inhibition of oxidative stress, inflammation and apoptosis. Therefore, CRT represents a promising therapeutic method for improving the cardiotoxic side effects caused by ATO treatment, and additional clinical applications are possible, but warrant further investigation.