greenmedinfo--2020-10-02--Comparative study on anti-inflammatory effect of Lonicerae Japonicae Flos and Lonicerae Flos.

The aim of this paper was to observe the anti-inflammatory action and mechanism of Lonicerae Japonicae Flos extract and Lonicerae Flos extract in xylene-induced ear swelling experiment and lipopolysaccharide ( LPS ) -induced RAW264.7 cell inflammatory model .
In vivo , xylene-induced mouse auricle swelling model was used to detect the auricle swelling degree and swelling inhibition rate of Lonicerae Japonicae Flos extract and Lonicerae Flos extract ; the pathological changes of mice auricle were observed by hematoxylin eosin ( HE ) staining .
In vitro , RAW264.7 inflammatory cell model was induced by LPS , where the cytotoxic effects @ @ @ @ @ @ @ Flos extract on RAW264.7 cells were detected by CCK-8 method ; Griess method was used to detect the effect of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on nitric oxide ( NO ) production , and ELISA method was used to detect the content of inflammatory factors interleukin-6 ( IL-6 ) , IL-1β , and tumor necrosis factor-α ( TNF-α ) .
At last , Western blot was used to detect the protein changes of cyclooxygenase 1 ( COX1 ) , COX2 and inducible nitric oxide synthetase ( iNOS ) for RAW264.7 @ @ @ @ @ @ @ Lonicerae Japonicae Flos extract and Lonicerae Flos extract could significantly inhibit the degree of auricle swelling caused by xylene in mice and the inhibition rate was positively correlated with the drug dose .
Furthermore , both of them could reduce the infiltration of lymphocytes and neutrophils in mouse ear tissues .
For in vitro experiments , both Lonicerae Japonicae Flos extract and Lonicerae Flos extract inhibited NO secretion in RAW264.7 cells , down-regulated the release of IL-1β , IL-6 and TNF-α , and down-regulated iNOS protein and COX2 , NF-κB p65 protein content @ @ @ @ @ @ @ Flos extract and Lonicerae Flos extract have good anti-inflammatory effect , and the mechanism may be related with the inhibition of NF-κB signaling pathway .

The aim of this paper was to observe the anti-inflammatory action and mechanism of Lonicerae Japonicae Flos extract and Lonicerae Flos extract in xylene-induced ear swelling experiment and lipopolysaccharide(LPS)-induced RAW264.7 cell inflammatory model. In vivo, xylene-induced mouse auricle swelling model was used to detect the auricle swelling degree and swelling inhibition rate of Lonicerae Japonicae Flos extract and Lonicerae Flos extract; the pathological changes of mice auricle were observed by hematoxylin eosin(HE) staining. In vitro, RAW264.7 inflammatory cell model was induced by LPS, where the cytotoxic effects of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on RAW264.7 cells were detected by CCK-8 method; Griess method was used to detect the effect of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on nitric oxide(NO) production, and ELISA method was used to detect the content of inflammatory factors interleukin-6(IL-6), IL-1β, and tumor necrosis factor-α(TNF-α). At last, Western blot was used to detect the protein changes of cyclooxygenase 1(COX1), COX2 and inducible nitric oxide synthetase(iNOS) for RAW264.7 cells. The results showed that both Lonicerae Japonicae Flos extract and Lonicerae Flos extract could significantly inhibit the degree of auricle swelling caused by xylene in mice and the inhibition rate was positively correlated with the drug dose. Furthermore, both of them could reduce the infiltration of lymphocytes and neutrophils in mouse ear tissues. For in vitro experiments, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract inhibited NO secretion in RAW264.7 cells, down-regulated the release of IL-1β, IL-6 and TNF-α, and down-regulated iNOS protein and COX2, NF-κB p65 protein content. In conclusion, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract have good anti-inflammatory effect, and the mechanism may be related with the inhibition of NF-κB signaling pathway.


greenmedinfo--2020-10-02--Changes in chemical components and antitumor activity during the heating process of Fructus Arctii.

The dried fruits ofL .
have been used in two forms in traditional Chinese medicine ; crude and stir-heating Fructus Arctii .
However , its processed product possesses better activity.In this study , the chemical constituents of both crude and processed Fructus Arctii and their antiproliferative activities were evaluated.The seven main active components in crude and various processed Fructus Arctii were quantitatively determined using high-performance liquid chromatography ( HPLC ) .
According to the actual amount in crude and five processed samples , seven single components were combined as multi-component combinations with six different proportions .
The antiproliferative activities of @ @ @ @ @ @ @ the CCK-8 assay.During the heating process , the proportion of the seven main components changed dynamically .
The contents of 3-caffeoylquinic acid ( 3-CQA ) , 3,5-dicaffeoylquinic acid ( 3,5-diCQA ) , and arctiin ( ARC ) declined , while the contents of 4-caffeoylquinic acid ( 4-CQA ) , 3,4-dicaffeoylquinic acid ( 3,4-diCQA ) , 4,5-dicaffeoylquinic acid ( 4,5-diCQA ) , and arctigenin ( ARG ) increased very significantly.The results also indicated that seven components in the processed samples had higher cytotoxic profiles against HL-60 cells than those in the crude sample .
@ @ @ @ @ @ @ the antitumor activity of Fructus Arctii by changing the proportion of active components .

The dried fruits ofL. have been used in two forms in traditional Chinese medicine; crude and stir-heating Fructus Arctii. However, its processed product possesses better activity.In this study, the chemical constituents of both crude and processed Fructus Arctii and their antiproliferative activities were evaluated.The seven main active components in crude and various processed Fructus Arctii were quantitatively determined using high-performance liquid chromatography (HPLC). According to the actual amount in crude and five processed samples, seven single components were combined as multi-component combinations with six different proportions. The antiproliferative activities of these compatibility component groups were examined using the CCK-8 assay.During the heating process, the proportion of the seven main components changed dynamically. The contents of 3-caffeoylquinic acid (3-CQA), 3,5-dicaffeoylquinic acid (3,5-diCQA), and arctiin (ARC) declined, while the contents of 4-caffeoylquinic acid (4-CQA), 3,4-dicaffeoylquinic acid (3,4-diCQA), 4,5-dicaffeoylquinic acid (4,5-diCQA), and arctigenin (ARG) increased very significantly.The results also indicated that seven components in the processed samples had higher cytotoxic profiles against HL-60 cells than those in the crude sample. Therefore, the heating process may enhance the antitumor activity of Fructus Arctii by changing the proportion of active components.


greenmedinfo--2020-10-02--Arctigenin attenuates diabetic kidney disease through the activation of PP2A in podocytes.

Arctigenin ( ATG ) is a major component of Fructus Arctii , a traditional herbal remedy that reduced proteinuria in @ @ @ @ @ whether ATG specifically provides renoprotection in DKD is not known .
Here we report that @ @ @ @ @ attenuate proteinuria and podocyte injury in mouse models of diabetes .
Transcriptomic analysis of diabetic @ @ @ @ @ adhesion and inflammation are two key pathways affected by ATG treatment , and mass spectrometry @ @ @ @ @ A ( PP2A ) as one of the top ATG-interacting proteins in renal cells .
@ @ @ @ @ reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with @ @ @ @ @ Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection .
Collectively , @ @ @ @ @ mechanism of ATG via PP2Aactivation and establish PP2A as a potential target for DKD progression @

Arctigenin (ATG) is a major component of Fructus Arctii, a traditional herbal remedy that reduced proteinuria in diabetic patients. However, whether ATG specifically provides renoprotection in DKD is not known. Here we report that ATG administration is sufficient to attenuate proteinuria and podocyte injury in mouse models of diabetes. Transcriptomic analysis of diabetic mouse glomeruli showed that cell adhesion and inflammation are two key pathways affected by ATG treatment, and mass spectrometry analysis identified protein phosphatase 2 A (PP2A) as one of the top ATG-interacting proteins in renal cells. Enhanced PP2A activity by ATG reduces p65 NF-κB-mediated inflammatory response and high glucose-induced migration in cultured podocytes via interaction with Drebrin-1. Importantly, podocyte-specific Pp2a deletion in mice exacerbates DKD injury and abrogates the ATG-mediated renoprotection. Collectively, our results demonstrate a renoprotective mechanism of ATG via PP2Aactivation and establish PP2A as a potential target for DKD progression.


greenmedinfo--2020-10-02--Total lignans from Fructus arctii has a preventive and therapeutic effect on diabetic retinopathy.

ETHNOPHARMACOLOGICAL RELEVANCE : Fructus Arctii is the dried ripe fruit of Arctium lappa L. ( family Asteraceae ) .
It is a well-known Chinese Materia Medica that was included in the Chinese pharmacopoeia because of its traditional therapeutic actions , such as heat removal , detoxification , and elimination of swelling .
Since ancient times Fructus Arctii has been used extensively in a number of classical drug formulas to treat type 2 diabetes mellitus .
Modern pharmacological studies have shown that certain components of Fructus Arctii have multiple physiological activities on type 2 diabetes and its complications .
AIM OF @ @ @ @ @ @ @ inhibitory effect of total lignans from Fructus Arctii ( TLFA ) on aldose reductase , the key enzyme in the polyol pathway , which is considered to be closely related to the onset of diabetic retinopathy ( DR ) .
The present study aimed to observe the preventive and therapeutic effects of TLFA on DR in Streptozotocin ( STZ ) -induced DR rats .
MATERIALS AND METHODS : TLFA was prepared from Fructus Arctii and its content was determined using UV spectrophotometry .
The DR model was induced by STZ in Wistar rats @ @ @ @ @ @ @ were gavaged once daily for 9 weeks with TLFA ( 1.38 , 0.69 , and 0.35 g/kg/day ) as soon as they were confirmed as diabetes models .
Pathological changes to retinal tissues and the expression of vascular endothelial growth factor ( VEGF ) and protein kinase C ( PKC ) in the retina were detected after TLFA treatment .
The effects of TLFA on blood glucose levels and body weight were also observed .
For DR treatment , the animals were gavaged once daily for 12 weeks with TLFA ( 1.38 and @ @ @ @ @ @ @ they were confirmed as diabetes models .
The therapeutic effect was studied using quantitative detection of blood-retina barrier ( BRB ) breakdown via an Evans Blue leakage assay .
RESULTS : For DR prevention , after 9 weeks of TLFA administration , histopathological examination of retinal tissue showed that TLFA improved the lesions in the retina .
Changes to retinal microstructures such as capillaries , ganglion cells , bipolar cells , and the membrane disk examined by electron microscopy further confirmed that TLFA has a preventive effect on retinopathy .
Terminal deoxynucleotidyl Transferase-mediated @ @ @ @ @ @ @ detection showed that TLFA could inhibit retinal cell apoptosis in the diabetic rats , and fasting blood glucose ( FBG ) levels of rats in the TLFA-treated groups decreased during the experiment .
For DR treatment , after 3 months of administration , the amount of dye leakage in the TLFA-administered groups was reduced by more than 50 % compared with that in the model group , which indicated that TLFA has a therapeutic effect on middle and late DR. Messenger RNA ( mRNA ) expression of VEGF and PKCβ2 in the retina @ @ @ @ @ @ @ chain reaction ( FQ-RT-PCR ) showed that TLFA could inhibit the expression of them , which was consistent with the results of immunohistochemistry ( IHC ) .
CONCLUSION : TLFA has a preventive and therapeutic effect on DR. Its mechanism of action on DR is related to inhibiting PKC activation and blocking VEGF elevation .

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus Arctii is the dried ripe fruit of Arctium lappa L. (family Asteraceae). It is a well-known Chinese Materia Medica that was included in the Chinese pharmacopoeia because of its traditional therapeutic actions, such as heat removal, detoxification, and elimination of swelling. Since ancient times Fructus Arctii has been used extensively in a number of classical drug formulas to treat type 2 diabetes mellitus. Modern pharmacological studies have shown that certain components of Fructus Arctii have multiple physiological activities on type 2 diabetes and its complications.
AIM OF THE STUDY: We have reported the inhibitory effect of total lignans from Fructus Arctii (TLFA) on aldose reductase, the key enzyme in the polyol pathway, which is considered to be closely related to the onset of diabetic retinopathy (DR). The present study aimed to observe the preventive and therapeutic effects of TLFA on DR in Streptozotocin (STZ)-induced DR rats.
MATERIALS AND METHODS: TLFA was prepared from Fructus Arctii and its content was determined using UV spectrophotometry. The DR model was induced by STZ in Wistar rats. For DR prevention, the animals were gavaged once daily for 9 weeks with TLFA (1.38, 0.69, and 0.35 g/kg/day) as soon as they were confirmed as diabetes models. Pathological changes to retinal tissues and the expression of vascular endothelial growth factor (VEGF) and protein kinase C (PKC) in the retina were detected after TLFA treatment. The effects of TLFA on blood glucose levels and body weight were also observed. For DR treatment, the animals were gavaged once daily for 12 weeks with TLFA (1.38 and 0.69 g/kg/day) at 3 months after they were confirmed as diabetes models. The therapeutic effect was studied using quantitative detection of blood-retina barrier (BRB) breakdown via an Evans Blue leakage assay.
RESULTS: For DR prevention, after 9 weeks of TLFA administration, histopathological examination of retinal tissue showed that TLFA improved the lesions in the retina. Changes to retinal microstructures such as capillaries, ganglion cells, bipolar cells, and the membrane disk examined by electron microscopy further confirmed that TLFA has a preventive effect on retinopathy. Terminal deoxynucleotidyl Transferase-mediated dUTP nick end labeling (TUNEL) detection showed that TLFA could inhibit retinal cell apoptosis in the diabetic rats, and fasting blood glucose (FBG) levels of rats in the TLFA-treated groups decreased during the experiment. For DR treatment, after 3 months of administration, the amount of dye leakage in the TLFA-administered groups was reduced by more than 50% compared with that in the model group, which indicated that TLFA has a therapeutic effect on middle and late DR. Messenger RNA (mRNA) expression of VEGF and PKCβ2 in the retina detected by real-time fluorescent quantitative reverse transcription-polymerase chain reaction (FQ-RT-PCR) showed that TLFA could inhibit the expression of them, which was consistent with the results of immunohistochemistry (IHC).
CONCLUSION: TLFA has a preventive and therapeutic effect on DR. Its mechanism of action on DR is related to inhibiting PKC activation and blocking VEGF elevation.


greenmedinfo--2020-10-02--Natural lignans from Arctium lappa as antiaging agents in Caenorhabditis elegans.

Arctium lappa is a well-known traditional medicinal plant in China ( TCM ) and Europe that has been used for thousands of years to treat arthritis , baldness or cancer .
The plant produces lignans as secondary metabolites , which have a wide range of bioactivities .
Yet , their antiaging potential has not been explored .
In this study , we isolated six lignans from A. lappa seeds , namely arctigenin , matairesinol , arctiin , ( iso ) lappaol A , lappaol C , and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied @ @ @ @ @ @ @ model .
All lignans at concentrations of 10 and 100μM significantly extended the mean life span of C. elegans .
The strongest effect was observed with matairesinol , which at a concentration of 100 μM extended the life span of worms by 25 % .
Additionally , we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress .
Furthermore , the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression , @ @ @ @ @ @ @ the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway .
All lignans up-regulated the expression of jnk-1 , indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade .
Our study reports new antiaging activities of lignans , which might be candidates for developing antiaging agents .

Arctium lappa is a well-known traditional medicinal plant in China (TCM) and Europe that has been used for thousands of years to treat arthritis, baldness or cancer. The plant produces lignans as secondary metabolites, which have a wide range of bioactivities. Yet, their antiaging potential has not been explored. In this study, we isolated six lignans from A. lappa seeds, namely arctigenin, matairesinol, arctiin, (iso)lappaol A, lappaol C, and lappaol F. The antioxidant and antiaging properties of the isolated lignans were studied using Caenorhabditis elegans as a relevant animal model. All lignans at concentrations of 10 and 100μM significantly extended the mean life span of C. elegans. The strongest effect was observed with matairesinol, which at a concentration of 100 μM extended the life span of worms by 25%. Additionally, we observed that five lignans are strong free radical-scavengers in vitro and in vivo and all lignans can improve survival of C. elegans under oxidative stress. Furthermore, the lignans can induce the nuclear translocation of the transcription factor DAF-16 and up-regulate its expression, suggesting that a possible underlying mechanism of the observed longevity-promoting activity of lignans depends on DAF-16 mediated signaling pathway. All lignans up-regulated the expression of jnk-1, indicating that lignans may promote the C. elegans longevity and stress resistance through a JNK-1-DAF-16 cascade. Our study reports new antiaging activities of lignans, which might be candidates for developing antiaging agents.


greenmedinfo--2020-10-02--An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonic

An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE : Lonicerae japonicae flos ( LJF , the dried flower bud or newly bloomed flower of Lonicera japonica Thunb . )
, a typical herbal medicine , targets the lung , heart and stomach meridian with the function of clearing heat and detoxication .
It ameliorated inflammatory responses and protected against acute lung inflammation in animal models .
Acute lung injury ( ALI ) is a kind of inflammatory disease in which alveolar cells are damaged .
However , a network pharmacology study to thoroughly investigate the mechanisms preventing ALI has not been performed .
AIM OF THE @ @ @ @ @ @ @ examined the main active ingredients in LJF and the protective effects of LJF on LPS-induced ALI in rats .
MATERIALS AND METHODS : First , the main active ingredients of LJF were screened in the TCMSP database , and the ALI-associated targets were collected from the GeneCards database .
Then , we used compound-target and target-pathway networks to uncover the preventive mechanisms of LJF .
Furthermore , we assessed the preventive effects of LJF in an LPS-induced rat model with the RNA-Seq technique to validate the possible molecular mechanisms of the effects of @ @ @ @ @ @ @ RESULTS : The network pharmacology results identified 28 main active compounds in LJF , and eight chemical components highly related to the potential targets , which were potential active compounds in LJF .
In all , 94 potential targets were recognized , including IL6 , TNF , PTGS2 , APP , F2 , and GRM5 .
The pathways revealed that the possible targets of LJF involved in the regulation of the IL-17 signalling pathway .
Then , in vivo experiments indicated that LJF decreased the levels of proinflammatory cytokines ( TNF- , IL-1 @ @ @ @ @ @ @ bronchoalveolar lavage fluid , decreased the levels of oxidative stress factors ( MDA and MPO ) and increased the activities of SOD and GSH-Px in lung tissue .
The RNA-Seq results revealed that 7811 , 775 and 3654 differentially expressed genes ( DEGs ) in Ctrl ( control group ) , ALI-LJF ( Lonicerae japonicae flos group ) and ALI-DXSM ( dexamethasone group ) , respectively .
KEGG pathway analysis showed that the DEGs associated with immune response and inflammation signalling pathways and the IL-17 signalling pathway were significantly enriched in LJF .
@ @ @ @ @ @ @ expression of CXCL2 , CXCL1 , CXCL6 , NFKBIA , IFNG , IL6 , IL17A , IL17F , IL17C , MMP9 and TNFAIP3 , which are involved in the IL-17 signalling pathway , were significantly decreased in the LJF group according to the qRT-PCR analyses .
CONCLUSIONS : In view of the network pharmacology and RNA-Seq results , the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI , which suggests directions for further research on LJF .

ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae japonicae flos (LJF, the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.), a typical herbal medicine, targets the lung, heart and stomach meridian with the function of clearing heat and detoxication. It ameliorated inflammatory responses and protected against acute lung inflammation in animal models. Acute lung injury (ALI) is a kind of inflammatory disease in which alveolar cells are damaged. However, a network pharmacology study to thoroughly investigate the mechanisms preventing ALI has not been performed.
AIM OF THE STUDY: In this study, we examined the main active ingredients in LJF and the protective effects of LJF on LPS-induced ALI in rats.
MATERIALS AND METHODS: First, the main active ingredients of LJF were screened in the TCMSP database, and the ALI-associated targets were collected from the GeneCards database. Then, we used compound-target and target-pathway networks to uncover the preventive mechanisms of LJF. Furthermore, we assessed the preventive effects of LJF in an LPS-induced rat model with the RNA-Seq technique to validate the possible molecular mechanisms of the effects of LJF in the treatment of ALI.
RESULTS: The network pharmacology results identified 28 main active compounds in LJF, and eight chemical components highly related to the potential targets, which were potential active compounds in LJF. In all, 94 potential targets were recognized, including IL6, TNF, PTGS2, APP, F2, and GRM5. The pathways revealed that the possible targets of LJF involved in the regulation of the IL-17 signalling pathway. Then, in vivo experiments indicated that LJF decreased the levels of proinflammatory cytokines (TNF-, IL-1, and IL-6) in serum and bronchoalveolar lavage fluid, decreased the levels of oxidative stress factors (MDA and MPO) and increased the activities of SOD and GSH-Px in lung tissue. The RNA-Seq results revealed that 7811, 775 and 3654 differentially expressed genes (DEGs) in Ctrl (control group), ALI-LJF (Lonicerae japonicae flos group) and ALI-DXSM (dexamethasone group), respectively. KEGG pathway analysis showed that the DEGs associated with immune response and inflammation signalling pathways and the IL-17 signalling pathway were significantly enriched in LJF. Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses.
CONCLUSIONS: In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF.


greenmedinfo--2020-10-02--Lonicera japonica polysaccharide improved behavioral changes and neuronal loss associated with LPS-i

Lonicera japonica polysaccharide improved behavioral changes and neuronal loss associated with LPS-induced learning and memory impairments.

BACKGROUND : Learning and memory impairments are important indexes in assessing Alzheimer 's disease ( AD ) .
Lonicera japonica ( L. japonica ) , a traditional Chinese herbal medicine , inhibits inflammation , but its role in neuroprotection is unclear .
Polysaccharide is the main active ingredient in L. japonica .
Here , we aimed to validate the effects of L. japonica polysaccharide ( LJP ) on lipopolysaccharide ( LPS ) -induced cognitive impairment and the underlying mechanism .
METHODS : The Chinese medicine system pharmacology database and analysis platform was used to predict the target of L. japonica @ @ @ @ @ @ @ predict the AD target .
We also performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathway enrichment analyses .
Experiments were performed after bioinformatic analysis for verification .
A chronic learning and memory impairment model was established by a single administration of LPS .
Learning and memory abilities of Kunming mice were examined after 7 days of induction .
The protective effects of LJP on LPS-induced impairment were investigated .
Neuronal damage was observed by Nissl staining .
Key proteins involved in the autophagy pathway were examined .
@ @ @ @ @ @ @ were 151 genes in the intersection of the target and ADrelated genes , and KEGG analysis suggested that these genes may act via multiple pathways .
LPS-induced changes in learning and memory in mice were significantly attenuated by LJP .
Nissl staining revealed that the neurons in the control group were lost and cellular arrangement was disrupted .
LJP alleviated the pathological changes in the neurons of mice .
The autophagy pathway was selected to verify the mechanism .
ATG5 , Beclin 1 , Vps34 , and LC3 II expression in the LPS @ @ @ @ @ @ @ was further increased in the LJP group .
CONCLUSIONS : LJP improved behavioral changes and neuronal loss associated with LPS-induced learning and memory impairments .
The underlying mechanism may be related to the regulation of the autophagy pathways .

BACKGROUND: Learning and memory impairments are important indexes in assessing Alzheimer's disease (AD). Lonicera japonica (L. japonica), a traditional Chinese herbal medicine, inhibits inflammation, but its role in neuroprotection is unclear. Polysaccharide is the main active ingredient in L. japonica. Here, we aimed to validate the effects of L. japonica polysaccharide (LJP) on lipopolysaccharide (LPS)-induced cognitive impairment and the underlying mechanism.
METHODS: The Chinese medicine system pharmacology database and analysis platform was used to predict the target of L. japonica; the GeneCards system was used to predict the AD target. We also performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Experiments were performed after bioinformatic analysis for verification. A chronic learning and memory impairment model was established by a single administration of LPS. Learning and memory abilities of Kunming mice were examined after 7 days of induction. The protective effects of LJP on LPS-induced impairment were investigated. Neuronal damage was observed by Nissl staining. Key proteins involved in the autophagy pathway were examined.
RESULTS: Bioinformatic analysis showed that there were 151 genes in the intersection of the target and ADrelated genes, and KEGG analysis suggested that these genes may act via multiple pathways. LPS-induced changes in learning and memory in mice were significantly attenuated by LJP. Nissl staining revealed that the neurons in the control group were lost and cellular arrangement was disrupted. LJP alleviated the pathological changes in the neurons of mice. The autophagy pathway was selected to verify the mechanism. ATG5, Beclin 1, Vps34, and LC3 II expression in the LPS group was significantly increased, and it was further increased in the LJP group.
CONCLUSIONS: LJP improved behavioral changes and neuronal loss associated with LPS-induced learning and memory impairments. The underlying mechanism may be related to the regulation of the autophagy pathways.


greenmedinfo--2020-10-02--Arctigenin could be used to reduce the risk of colitis-associated cancer in patients with colitis.

Arctigenin , the major active constituent of Fructus Arctii , has been reported to inhibit the growth of various tumors and alleviate colitis .
This study aimed to prove the protective effect of arctigenin on colitis-associated cancer ( CAC ) and explore its mechanisms .
Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane ( AOM ) /dextran sulfate sodium ( DSS ) -induced CAC mice .
Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation ( FAO ) metabolism in macrophages , as determined by untargeted metabolomics .
Arctigenin also inhibited the expression @ @ @ @ @ @ @ , reduced the acetylation ofα-tubulin , and disrupted NLRP3 complex formation , which in turn inactivated the NLRP3 inflammasome .
Downregulation of the CPT1-FAO-acetyl-coenzyme A ( acetyl-CoA ) -acetylated α-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly , as confirmed by CPT1 overexpression .
Lastly , arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice , and the effect was significantly diminished by the overexpression of adeno-associated virus ( AAV ) 9-CPT1 .
Taken together , these results show that the inhibition of @ @ @ @ @ @ @ downregulation contributes to the preventative effect of arctigenin against CAC .
Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis .

Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associated cancer (CAC) and explore its mechanisms. Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mice. Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation (FAO) metabolism in macrophages, as determined by untargeted metabolomics. Arctigenin also inhibited the expression of carnitine palmitoyltransferase 1 (CPT1), reduced the acetylation ofα-tubulin, and disrupted NLRP3 complex formation, which in turn inactivated the NLRP3 inflammasome. Downregulation of the CPT1-FAO-acetyl-coenzyme A (acetyl-CoA)-acetylated α-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly, as confirmed by CPT1 overexpression. Lastly, arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice, and the effect was significantly diminished by the overexpression of adeno-associated virus (AAV)9-CPT1. Taken together, these results show that the inhibition of NLRP3 inflammasome assembly inmacrophages due to FAO downregulation contributes to the preventative effect of arctigenin against CAC. Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis.


greenmedinfo--2020-10-02--Arctigenin protects against depression by inhibiting microglial activation and neuroinflammation.

BACKGROUND AND PURPOSE : Arctigenin ( AG ) , a major bioactive component of Fructus arctii , has been reported to have antidepressant-like effects .
However , the precise mechanism of AG as an antidepressant is still unclear .
Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 ( HMGB1 ) /TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways , leading to depression .
In this study , we have investigated the antidepressant mechanism of AG by conducting in vitro and in vivo studies .
EXPERIMENTAL APPROACH : The antidepressant-like effects of AG were tested @ @ @ @ @ @ @ CUMS ) -induced model of depression in mice .
The effects of CUMS on TLR4mice were examined .
The action of AG on HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways in the prefrontal cortex ( PFC ) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia .
The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without AG was examined by LSPR and co-immunoprecipitation assays .
KEY RESULTS : AG exhibited antidepressant-like effects .
Immobility times in the TST and FST were reduced in TLR4mice compared with WT mice .
AG @ @ @ @ @ @ @ the PFC of the mouse brain .
AG inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions .
AG suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways .
CONCLUSIONS AND IMPLICATIONS : Our results provide the first evidence that AG has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways .
This suggests that AG has potential as a new drug candidate suitable for clinical trials to treat depression .

BACKGROUND AND PURPOSE: Arctigenin (AG), a major bioactive component of Fructus arctii, has been reported to have antidepressant-like effects. However, the precise mechanism of AG as an antidepressant is still unclear. Neuroinflammation can be caused by excessive production of proinflammatory cytokines in microglia via high-mobility group box 1 (HMGB1)/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways, leading to depression. In this study, we have investigated the antidepressant mechanism of AG by conducting in vitro and in vivo studies.
EXPERIMENTAL APPROACH: The antidepressant-like effects of AG were tested using the chronic unpredictable mild stress (CUMS)-induced model of depression in mice. The effects of CUMS on TLR4mice were examined. The action of AG on HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways in the prefrontal cortex (PFC) of mouse brain and HMGB1- or TNF-α-stimulated primary cultured microglia. The interaction between HMGB1 and TLR4 or TNF-α and TNFR1 with or without AG was examined by LSPR and co-immunoprecipitation assays.
KEY RESULTS: AG exhibited antidepressant-like effects. Immobility times in the TST and FST were reduced in TLR4mice compared with WT mice. AG inhibited microglia activation, inflammatory responses in the PFC of the mouse brain. AG inhibited HMGB1 and TLR4 or TNF-α and TNFR1 interactions. AG suppressed both HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signaling pathways.
CONCLUSIONS AND IMPLICATIONS: Our results provide the first evidence that AG has antidepressant-like effects by attenuating excessive microglial activation and neuroinflammation through the HMGB1/TLR4/NF-κB and TNF-α/TNFR1/NF-κB signalling pathways. This suggests that AG has potential as a new drug candidate suitable for clinical trials to treat depression.


greenmedinfo--2020-10-02--Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arc

Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa.

Arctigenin ( AR ) and its glycoside , arctiin , are two major active ingredients of Arctium lappa L ( A lappa ) , a popular medicinal herb and health supplement frequently used in Asia .
In the past several decades , bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects .
In the current article , we aimed to provide an overview of the pharmacology of AR and arctiin , focusing on their anti-inflammatory effects , pharmacokinetics properties and clinical efficacies .
Compared to acrtiin , AR was reported as the @ @ @ @ @ @ @ in the majority of studies .
AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase ( iNOS ) via modulation of several cytokines .
Due to its potent anti-inflammatory effects , AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases .
However , pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver , intestine and plasma , which might hinder its in vivo and clinical efficacy after oral administration .
Based on the reviewed pharmacological and pharmacokinetic characteristics of AR , @ @ @ @ @ @ @ via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa .

Arctigenin (AR) and its glycoside, arctiin, are two major active ingredients of Arctium lappa L (A lappa), a popular medicinal herb and health supplement frequently used in Asia. In the past several decades, bioactive components from A lappa have attracted the attention of researchers due to their promising therapeutic effects. In the current article, we aimed to provide an overview of the pharmacology of AR and arctiin, focusing on their anti-inflammatory effects, pharmacokinetics properties and clinical efficacies. Compared to acrtiin, AR was reported as the most potent bioactive component of A lappa in the majority of studies. AR exhibits potent anti-inflammatory activities by inhibiting inducible nitric oxide synthase (iNOS) via modulation of several cytokines. Due to its potent anti-inflammatory effects, AR may serve as a potential therapeutic compound against both acute inflammation and various chronic diseases. However, pharmacokinetic studies demonstrated the extensive glucuronidation and hydrolysis of AR in liver, intestine and plasma, which might hinder its in vivo and clinical efficacy after oral administration. Based on the reviewed pharmacological and pharmacokinetic characteristics of AR, further pharmacokinetic and pharmacodynamic studies of AR via alternative administration routes are suggested to promote its ability to serve as a therapeutic agent as well as an ideal bioactive marker for A lappa.


greenmedinfo--2020-10-02--Arctiin prevents LPS-induced acute lung injury via inhibition of PI3K/AKT signaling pathway.

Arctiin is a lignin isolated from Arctium lappa which has been known to have anti-viral and anti-inflammatory effects .
The aim of this study is to explore the protective effect of arctiin on lipopolysaccharide ( LPS ) -induced inflammatory responses in acute lung injury ( ALI ) model of mice .
Male BALB/c mice were pretreated with commercial arctiin ( 10 , 20 , and 40 mg/kg ) 1 h prior to LPS challenge .
Twelve hours later , airway inflammation was assessed .
We assessed the effects of arctiin on the LPS-induced production of TNF-α , IL-6 , and @ @ @ @ @ @ @ BALF ) .
The lung wet-to-dry weight ratio , myeloperoxidase ( MPO ) activity , and inflammatory signaling pathway were also detected .
Our results showed that arctiin not only significantly ameliorated LPS-stimulated lung histopathological changes but also reduced the lung MPO activity .
Arctiin also dramatically decreased the production of TNF-α , IL-1β , and IL-6 in the BALF .
In addition , arctiin significantly inhibited LPS-induced PI3K/Akt phosphorylation as well as NF-κB activation .
In conclusion , our results suggested that arctiin protected against LPS-induced ALI through inhibiting PI3K/AKT/NF-κB signaling pathway @

Arctiin is a lignin isolated from Arctium lappa which has been known to have anti-viral and anti-inflammatory effects. The aim of this study is to explore the protective effect of arctiin on lipopolysaccharide (LPS)-induced inflammatory responses in acute lung injury (ALI) model of mice. Male BALB/c mice were pretreated with commercial arctiin (10, 20, and 40 mg/kg) 1 h prior to LPS challenge. Twelve hours later, airway inflammation was assessed. We assessed the effects of arctiin on the LPS-induced production of TNF-α, IL-6, and IL-1β in the bronchoalveolar lavage fluid (BALF). The lung wet-to-dry weight ratio, myeloperoxidase (MPO) activity, and inflammatory signaling pathway were also detected. Our results showed that arctiin not only significantly ameliorated LPS-stimulated lung histopathological changes but also reduced the lung MPO activity. Arctiin also dramatically decreased the production of TNF-α, IL-1β, and IL-6 in the BALF. In addition, arctiin significantly inhibited LPS-induced PI3K/Akt phosphorylation as well as NF-κB activation. In conclusion, our results suggested that arctiin protected against LPS-induced ALI through inhibiting PI3K/AKT/NF-κB signaling pathway.


greenmedinfo--2020-10-02--Arctiin protects rat heart against ischemia/reperfusion injury.

RIPK1/RIPK3/MLKL ( Receptor-interacting protein kinase 1/Receptor-interacting protein kinase 3/Mixed lineage kinase domain-like protein ) pathway-mediated necroptosis contributes to myocardial ischemia/reperfusion ( I/R ) injury , and Arctiin can prevent myocardial fibrosis and hypertrophy .
This study aims to explore the effect of Arctiin on myocardial I/R injury and the underlying mechanisms .
SD rat hearts or cardiomyocytes were subjected to I/R or hypoxia/reoxygenation ( H/R ) to establish the I/R or H/R injury model .
The methods of biochemistry , PI/DAPI ( propidium iodide/4',6-Diamidino-2-Phenylindole ) and H & E ( Hematoxylin & eosin ) staining were used to evaluate the @ @ @ @ @ @ @ of Arctiin on necroptosis in I/R-treated hearts or H/R-treated cardiomyocytes were assessed .
The results showed that Arctiin reduced myocardial I/R injury ( decreases in myocardial infarction and creatine kinase release ) , concomitant with a decrease in levels of necroptosis-associated proteins ( RIPK1/p-RIPK1 , RIPK3/p-RIPK3 and MLKL/p-MLKL ) in I/R-treated rat hearts .
Consistently , the necrosis and LDH release in H/R-treated cardiomyocytes were attenuated in the presence of Arctiin , accompanied by suppression of necroptosis-relevant proteins .
Furthermore , H/R-induced reactive oxygen species ( ROS ) generation and mitochondrial dysfunctions ( @ @ @ @ @ @ @ in ATP production ) were impaired by Arctiin .
Using the program of the Molecular Operating Environment ( MOE ) , we predict that RIPK1 and MLKL ( but not RIPK3 ) might be the potential targets of Arctiin .
Based on these observations , we conclude that Arctiin can protect the rat heart from I/R injury , and its beneficial effect is related to reduction of necroptosis via scavenging reactive oxygen species and restoring mitochondrial functions or targeting RIPK1 and/or MLKL .

RIPK1/RIPK3/MLKL (Receptor-interacting protein kinase 1/Receptor-interacting protein kinase 3/Mixed lineage kinase domain-like protein) pathway-mediated necroptosis contributes to myocardial ischemia/reperfusion (I/R) injury, and Arctiin can prevent myocardial fibrosis and hypertrophy. This study aims to explore the effect of Arctiin on myocardial I/R injury and the underlying mechanisms. SD rat hearts or cardiomyocytes were subjected to I/R or hypoxia/reoxygenation (H/R) to establish the I/R or H/R injury model. The methods of biochemistry, PI/DAPI (propidium iodide/4',6-Diamidino-2-Phenylindole) and H&E (Hematoxylin&eosin) staining were used to evaluate the I/R or H/R injury. The effects of Arctiin on necroptosis in I/R-treated hearts or H/R-treated cardiomyocytes were assessed. The results showed that Arctiin reduced myocardial I/R injury (decreases in myocardial infarction and creatine kinase release), concomitant with a decrease in levels of necroptosis-associated proteins (RIPK1/p-RIPK1, RIPK3/p-RIPK3 and MLKL/p-MLKL) in I/R-treated rat hearts. Consistently, the necrosis and LDH release in H/R-treated cardiomyocytes were attenuated in the presence of Arctiin, accompanied by suppression of necroptosis-relevant proteins. Furthermore, H/R-induced reactive oxygen species (ROS) generation and mitochondrial dysfunctions (increase in mitochondrial membrane potential and decrease in ATP production) were impaired by Arctiin. Using the program of the Molecular Operating Environment (MOE), we predict that RIPK1 and MLKL (but not RIPK3) might be the potential targets of Arctiin. Based on these observations, we conclude that Arctiin can protect the rat heart from I/R injury, and its beneficial effect is related to reduction of necroptosis via scavenging reactive oxygen species and restoring mitochondrial functions or targeting RIPK1 and/or MLKL.


greenmedinfo--2020-10-02--Arctiin attenuates high glucose-induced human retinal capillary endothelial cell proliferation.

Diabetic retinopathy ( DR ) is one of the most prominent microvascular complications of diabetes , which remains the leading cause of legal blindness in the world .
Arctiin , a bioactive compound from Arctium lappa L. , has been reported to have antidiabetic activity .
In this study , we investigated the effect of arctiin on a human retinal capillary endothelial cell ( HRCEC ) line and how arctiin inhibits cell proliferation in high glucose ( HG ) -induced HRCECs .
Results showed that arctiin decreased HG-induced HRCECs proliferation in a dose-dependent manner by inducing cell cycle arrest at @ @ @ @ @ @ @ and immunofluorescence staining indicated that arctiin abrogated tube formation induced by HG-induced HRCECs in a dose-dependent manner via down-regulation of VEGF expression .
Mechanistic study indicated that perturbation of the ROCK1/PTEN/PI3K/Akt signalling pathway plays a vital role in the arctiin-mediated anti-proliferative effect .
Furthermore , pre-incubation of HRCECs with Y-27632 attenuated arctiin-induced cell cycle arrest , cell proliferation and tube formation inhibition .
Y-27632 also reversed the activation of PTEN , the inactivation/dephosphorylation of PI3K/Akt and down-regulation of VEGF .
Taken together , the results demonstrated that arctiin inhibits the proliferation of HG-induced @ @ @ @ @ @ @ PTEN and inactivation of PI3K and Akt , resulting in down-regulation of VEGF , which inhibits endothelial cell proliferation .

Diabetic retinopathy (DR) is one of the most prominent microvascular complications of diabetes, which remains the leading cause of legal blindness in the world. Arctiin, a bioactive compound from Arctium lappa L., has been reported to have antidiabetic activity. In this study, we investigated the effect of arctiin on a human retinal capillary endothelial cell (HRCEC) line and how arctiin inhibits cell proliferation in high glucose (HG)-induced HRCECs. Results showed that arctiin decreased HG-induced HRCECs proliferation in a dose-dependent manner by inducing cell cycle arrest at the G0/G1 phase. Tube formation assay and immunofluorescence staining indicated that arctiin abrogated tube formation induced by HG-induced HRCECs in a dose-dependent manner via down-regulation of VEGF expression. Mechanistic study indicated that perturbation of the ROCK1/PTEN/PI3K/Akt signalling pathway plays a vital role in the arctiin-mediated anti-proliferative effect. Furthermore, pre-incubation of HRCECs with Y-27632 attenuated arctiin-induced cell cycle arrest, cell proliferation and tube formation inhibition. Y-27632 also reversed the activation of PTEN, the inactivation/dephosphorylation of PI3K/Akt and down-regulation of VEGF. Taken together, the results demonstrated that arctiin inhibits the proliferation of HG-induced HRCECs through the activation of ROCK1 and PTEN and inactivation of PI3K and Akt, resulting in down-regulation of VEGF, which inhibits endothelial cell proliferation.


greenmedinfo--2020-10-02--Enhancement of the apoptotic effects of Arctii fructus extracts on cancer cells by the enzymatic bio

Enhancement of the apoptotic effects of Arctii fructus extracts on cancer cells by the enzymatic bioconversion of lignans.

The fruit ofL .
( Arctii Fructus ) is one of the most popularly used medicinal plant components in Asia @ @ @ @ @ of Arctii Fructus extract , a bioconversion method was developed to produce arctigenin from arctiin @ @ @ @ @ arctigenin content by > 5 fold in Arctii Fructus extracts .
The bioconversion products enhanced @ @ @ @ @ .
The cell viabilities of gefitinib-resistant lung cancer HCC827 ( HCC827GR ) cells and colon @ @ @ @ @ were decreased by 40 % and 35 % , respectively .
The bioconversion products also @ @ @ @ @ cells .
In addition , the increase of apoptosis in cancer cells by bioconversion was @ @ @ @ @ analysis .
These results indicated that arctigenin exerts anticancer effects on lung and colon cancer @ @ @ @ @ can potentially function as a chemopreventive agent .
In addition , bioconverted Arctii Fructus extract @ @ @ @ @ the same levels of purified arctigenin , indicating the advantage of consuming Arctii Fructus itself @ @ @ @ @ material .

The fruit ofL. (Arctii Fructus) is one of the most popularly used medicinal plant components in Asia. To enhance the functionality of Arctii Fructus extract, a bioconversion method was developed to produce arctigenin from arctiin. Treatment withβ-glucosidase increased the arctigenin content by>5 fold in Arctii Fructus extracts. The bioconversion products enhanced the apoptosis of cancer cells. The cell viabilities of gefitinib-resistant lung cancer HCC827 (HCC827GR) cells and colon cancer cells (DLD1) were decreased by 40% and 35%, respectively. The bioconversion products also decreased anchorage-independent growth of cancer cells. In addition, the increase of apoptosis in cancer cells by bioconversion was confirmed by the flow cytometry analysis. These results indicated that arctigenin exerts anticancer effects on lung and colon cancer cells and that Arctii Fructus can potentially function as a chemopreventive agent. In addition, bioconverted Arctii Fructus extract displayed higher anticancer activity than the same levels of purified arctigenin, indicating the advantage of consuming Arctii Fructus itself as a food or medicinal material.


greenmedinfo--2020-10-02--Antidepressive effect of arctiin by attenuating neuroinflammation.

Inflammation is a potential factor in the pathophysiology of depression .
A traditional Chinese herbal medicine , arctiin , and its aglycone , arctigenin , are the major bioactive components inand exhibit neuroprotective and anti-inflammatory activities .
Arctigenin has been reported to have antidepressant-like effects .
However , the antidepressant-like effects of arctiin , its precursor , remain unknown .
In this study , we investigated the antidepressant-like effects of arctiin and its underlying mechanisms byandexperiments in mice .
Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests @ @ @ @ @ @ @ prefrontal cortex ( PFC ) of the brain .
Arctiin also attenuated the levels of three inflammatory mediators , indoleamine 2,3-dioxygenase , 5-hydroxytryptamine , and dopamine , that were elevated in the PFC or serum of chronic unpredictable mild stress ( CUMS ) -exposed mice .
Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 ( HMGB1 ) /toll-like receptor 4 ( TLR4 ) - and tumor necrosis factor-α ( TNF-α ) /TNF receptor 1 ( TNFR1 ) -mediated nuclear factor-kappa B ( NF-κB ) activation in @ @ @ @ @ @ @ or TNF-α-stimulated primary cultured microglia .
These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammationvia the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways .

Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components inand exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms byandexperiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammationvia the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.


greenmedinfo--2020-10-02--Arctiin may serve as a novel therapeutic agent for the treatment of osteoporosis.

Osteoporosis , characterized by disrupted bone resorption and formation , is viewed as a global health challenge .
Arctiin ( ARC ) is a main component of Arctium lappa L , which exerts chemopreventive effects against various tumor cells .
However , the role of ARC in bone remodeling is still unclear .
Here , we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand ( RANKL ) in a dose- and time-dependent manner without exerting cytotoxic effects .
Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated @ @ @ @ @ @ @ signaling pathways , but also enhances the expression of cytoprotective enzymes thatare involved in scavenging reactive oxygen species ( ROS ) .
Further , ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 ( NFATc1 ) during RANKL-induced osteoclast formation .
Preclinical studies showed that ARC protects bone loss in an ovariectomy ( OVX ) mouse model .
Conclusively , our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK , calcium , and NFATc1 signaling pathway , as well as by promoting @ @ @ @ @ @ @ Nrf2/Keap1/ARE signaling pathway , therebypreventing OVX-induced bone loss .
Thus , ARC may serve as a novel therapeutic agent for the treatment of osteoporosis .

Osteoporosis, characterized by disrupted bone resorption and formation, is viewed as a global health challenge. Arctiin (ARC) is a main component of Arctium lappa L, which exerts chemopreventive effects against various tumor cells. However, the role of ARC in bone remodeling is still unclear. Here, we first demonstrated that ARC inhibits osteoclast formation and bone resorption function induced by the receptor activator of nuclear factor-κB ligand (RANKL) in a dose- and time-dependent manner without exerting cytotoxic effects. Mechanistic analysis revealed that ARC not only suppresses RANKL-induced mitogen-activated protein kinase (MAPK) and calcium signaling pathways, but also enhances the expression of cytoprotective enzymes thatare involved in scavenging reactive oxygen species (ROS). Further, ARC inhibits the activation of the major transcription factor nuclear factor of activated T cells 1 (NFATc1) during RANKL-induced osteoclast formation. Preclinical studies showed that ARC protects bone loss in an ovariectomy (OVX) mouse model. Conclusively, our data confirmed that ARC could potentially inhibit osteoclastogenesis by abrogating RANKL-induced MAPK, calcium, and NFATc1 signaling pathway, as well as by promoting the expression of ROS scavenging enzymes in Nrf2/Keap1/ARE signaling pathway, therebypreventing OVX-induced bone loss. Thus, ARC may serve as a novel therapeutic agent for the treatment of osteoporosis.


greenmedinfo--2020-10-02--Structure-guided identification of black cohosh triterpenoids with in vitro activity against multipl

Structure-guided identification of black cohosh triterpenoids with in vitro activity against multiple myeloma.

Black cohosh is a well-established medicinal plant and preparations of its rootstock are used for the treatment of mild climacteric complaints .
The compounds considered responsible for the therapeutic effect are triterpene glycosides , characterized by a cycloartane scaffold and a pentose moiety .
Because some of these triterpenoids were found to exhibit relevant cytotoxic effects against human breast cancer cells , we decided to investigate their activity on multiple myeloma cell lines NCI-H929 , OPM-2 , and U266 .
In a systematic approach , we initially tested three known cytotoxic compounds of three different triterpenoid types , revealing the @ @ @ @ @ @ @ .
In a second round , seven naturally occurring cimigenol derivatives were compared with respect to their sugar moiety and their substitution pattern at position C-25 , leading to 25 -- methylcimigenol-3 -- α-L-arabinopyranoside as the most potent candidate .
Interestingly , not only the methyl group at position C-25 increased the cytotoxic effect but also the arabinose moiety at position C-3 had an impact on the activity .
The variety of cimigenol derivatives , moreover , allowed a detailed discussion oftheir structure-activity relationships , not only for their effect on multiple myeloma @ @ @ @ @ @ @ studies on the cytotoxicity of black cohosh triterpenoids .

Black cohosh is a well-established medicinal plant and preparations of its rootstock are used for the treatment of mild climacteric complaints. The compounds considered responsible for the therapeutic effect are triterpene glycosides, characterized by a cycloartane scaffold and a pentose moiety. Because some of these triterpenoids were found to exhibit relevant cytotoxic effects against human breast cancer cells, we decided to investigate their activity on multiple myeloma cell lines NCI-H929, OPM-2, and U266. In a systematic approach, we initially tested three known cytotoxic compounds of three different triterpenoid types, revealing the cimigenol-type triterpenoid as the most active constituent. In a second round, seven naturally occurring cimigenol derivatives were compared with respect to their sugar moiety and their substitution pattern at position C-25, leading to 25--methylcimigenol-3--α-L-arabinopyranoside as the most potent candidate. Interestingly, not only the methyl group at position C-25 increased the cytotoxic effect but also the arabinose moiety at position C-3 had an impact on the activity. The variety of cimigenol derivatives, moreover, allowed a detailed discussion oftheir structure-activity relationships, not only for their effect on multiple myeloma cells but also with regard to previous studies on the cytotoxicity of black cohosh triterpenoids.


greenmedinfo--2020-10-03--The anti-aging effects of astaxanthin were shown to be due in part to the Nrf2/Keap1 and NF-κB pathw

The anti-aging effects of astaxanthin were shown to be due in part to the Nrf2/Keap1 and NF-κB pathway.

As a potential antioxidant , astaxanthin ( AST ) exhibits anti-aging effects .
However , its relationships to oxidative stress and immunity have yet to be sufficiently investigated .
In this research , integrated analysis of oxidative stress and immunosenescence was performed to elucidate the efficacy and potential mechanisms of AST in d-galactose-induced aging in rats .
The results showed that AST significantly decreased malonaldehyde ( MDA ) levels and increased antioxidase activity , in addition to demonstrating the ability to repair histopathological injuries to the liver , thereby attenuating oxidative stress .
Nuclear factor erythroid 2-related factor 2 ( @ @ @ @ @ @ @ % , whereas Kelch-like ECH-associated protein-1 ( Keap1 ) expression was simultaneously down-regulated by 51.22 % .
Moreover , AST significantly reduced interleukin-1β ( IL-1β ) and interleukin-6 ( IL-6 ) levels , as well as expression of nuclear factor-kappa B ( NF-κB ) ( p65 ) and i-kappa-B-alpha ( IκBα ) proteins .
Findings of repair of immune organs , as well as elevated levels of interleukin-2 ( IL-2 ) , immunoglobulin M ( IgM ) and immunoglobulin G ( IgG ) , suggest a novel mechanism by which AST could regulate @ @ @ @ @ @ @ immunosenescence .
The anti-aging effects of AST were shown to be due in part to the Nrf2/Keap1 and NF-κB pathways , and AST treatment ameliorated oxidative stress and immune impairment overall .

As a potential antioxidant, astaxanthin (AST) exhibits anti-aging effects. However, its relationships to oxidative stress and immunity have yet to be sufficiently investigated. In this research, integrated analysis of oxidative stress and immunosenescence was performed to elucidate the efficacy and potential mechanisms of AST in d-galactose-induced aging in rats. The results showed that AST significantly decreased malonaldehyde (MDA) levels and increased antioxidase activity, in addition to demonstrating the ability to repair histopathological injuries to the liver, thereby attenuating oxidative stress. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression was up-regulated by 117.95%, whereas Kelch-like ECH-associated protein-1 (Keap1) expression was simultaneously down-regulated by 51.22%. Moreover, AST significantly reduced interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels, as well as expression of nuclear factor-kappa B (NF-κB) (p65) and i-kappa-B-alpha (IκBα) proteins. Findings of repair of immune organs, as well as elevated levels of interleukin-2 (IL-2), immunoglobulin M (IgM) and immunoglobulin G (IgG), suggest a novel mechanism by which AST could regulate cellular immunity and humoral immunity to attenuate immunosenescence. The anti-aging effects of AST were shown to be due in part to the Nrf2/Keap1 and NF-κB pathways, and AST treatment ameliorated oxidative stress and immune impairment overall.


greenmedinfo--2020-10-03--Absorbability of astaxanthin was much lower in obese mice than in normal mice.

Astaxanthin has been favored as a health food supplement by obese consumers .
However , no detailed descriptions are available @ @ @ @ @ in obese individuals .
In this study , we conducted acute and chronic feeding experiments @ @ @ @ @ the differences in astaxanthin absorption in normal and obese bodies .
The obesity condition greatly @ @ @ @ @ blood and liver , its accumulation in tissues and organs , and the bioaccessibility .
@ @ @ @ @ the excessive intake of sucrose , fatty acids , and cholesterol , the increased gastrointestinal @ @ @ @ @ of gut microbiota in the obese body .
Overall , our study showed that the @ @ @ @ @ less oral absorbability of astaxanthin than a normal body , and we suggest that the @ @ @ @ @ astaxanthin can be properly increased for the obese body in the hope that astaxanthin will @ @ @ @ @ in obese individuals .

Astaxanthin has been favored as a health food supplement by obese consumers. However, no detailed descriptions are available concerning the absorption of astaxanthin in obese individuals. In this study, we conducted acute and chronic feeding experiments in C57BL/6J mice to study the differences in astaxanthin absorption in normal and obese bodies. The obesity condition greatly decreased astaxanthin concentration in the blood and liver, its accumulation in tissues and organs, and the bioaccessibility. This may be related to the excessive intake of sucrose, fatty acids, and cholesterol, the increased gastrointestinal motility, and the disorder of gut microbiota in the obese body. Overall, our study showed that the obese body had a far less oral absorbability of astaxanthin than a normal body, and we suggest that the recommended or approved doses of astaxanthin can be properly increased for the obese body in the hope that astaxanthin will play a more active role in obese individuals.


greenmedinfo--2020-10-03--Protective effect of astaxanthin against SnS 2 nanoflowers induced testes toxicity.

The reproductive toxicity of SnSnanoflowers ( SnSNFs ) has been studied in our previous experiment , but the underlying mechanism is still not clear .
Astaxanthin ( ASX ) is a red carotenoid pigment with antioxidant , anticancer and anti-inflammatory properties , showing neuroprotective properties via its antioxidant capacity .
To examine the ASX effect on sub-chronic testis injury induced by SnSNFs , we randomly and equally divided 40 Kunming male mice into four groups ( control , ASX control , NF and NF + ASX groups ) .
Then , ASX dissolved in olive oil was administered intragastrically for @ @ @ @ @ @ @ ASX treatment improved the sperm parameters in mice .
Meanwhile , the ASX treatment significantly attenuated testis histopathological injury and ultrastructure alterationsinduced by SnSNFs .
It also alleviated testicular oxidative stress , inflammation , apoptosis and necroptosis in mice .
Furthermore , ASX markedly upregulated the expression of Bcl-2 and downregulated the expressions of Fas , FasL , RIPK1 , FADD , Bax , Cytochrome C , Caspase-9 , Cleaved Caspase-8 , Cleaved Caspase-3 , RIPK3 , MLKL and FLIP in the testis tissues compared with the NF group .
Therefore , ASX @ @ @ @ @ @ @ in mice , and the potential mechanism is associated with its ability to inhibit the oxidative stress , inflammatory response , testicular apoptosis and necroptosis , as well as downregulating in the expression of the RIPK1-RIPK3-MLKL signaling and mitochondrial related apoptosis genes .

The reproductive toxicity of SnSnanoflowers (SnSNFs) has been studied in our previous experiment, but the underlying mechanism is still not clear. Astaxanthin (ASX) is a red carotenoid pigment with antioxidant, anticancer and anti-inflammatory properties, showing neuroprotective properties via its antioxidant capacity. To examine the ASX effect on sub-chronic testis injury induced by SnSNFs, we randomly and equally divided 40 Kunming male mice into four groups (control, ASX control, NF and NF + ASX groups). Then, ASX dissolved in olive oil was administered intragastrically for 30 consecutive days. Results showed that ASX treatment improved the sperm parameters in mice. Meanwhile, the ASX treatment significantly attenuated testis histopathological injury and ultrastructure alterationsinduced by SnSNFs. It also alleviated testicular oxidative stress, inflammation, apoptosis and necroptosis in mice. Furthermore, ASX markedly upregulated the expression of Bcl-2 and downregulated the expressions of Fas, FasL, RIPK1, FADD, Bax, Cytochrome C, Caspase-9, Cleaved Caspase-8, Cleaved Caspase-3, RIPK3, MLKL and FLIP in the testis tissues compared with the NF group. Therefore, ASX had a markedly protective effect against SnSNFs in mice, and the potential mechanism is associated with its ability to inhibit the oxidative stress, inflammatory response, testicular apoptosis and necroptosis, as well as downregulating in the expression of the RIPK1-RIPK3-MLKL signaling and mitochondrial related apoptosis genes.


greenmedinfo--2020-10-03--Protective effects of astaxanthin on nephrotoxicity in rats with induced renovascular occlusion.

BACKGROUND : Various effects of Astaxanthin was shown in the studies including its antioxidant , anti-inflammatory , anti-tumor and immunregulator effects .
OBJECTIVE : The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms .
METHODS : The rats were randomly assigned into three groups as follows : Group 1 : control group ( n=12 ) , Group 2 : renal ischemiareperfusion injury group ( n=12 ) , Group 3 : renal ischemia-reperfusion + asthaxantine treated group ( n=12 ) .
The control group and @ @ @ @ @ @ @ olive oil for 7 days before establishing ischemia to renal tissue .
Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia .
Caspase- ( 3 , 8 , 9 ) , GSH , SOD , Total Thiol , TNF-α , IL-6 , 8-OHdG were performed for each group .
RESULTS : Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion .
Much less renal tubular damage was determined the IRI+ASX group in @ @ @ @ @ @ @ , -9 and -3 immunoreactivity was observed to be minimal in the control group .
Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to IRI group and close to the level of the control group ( p < 0.05 ) .
Caspase-3 levels of tissue samples were significantly increased in IRI group compared to other groups , but significantly lower in IRI+ASX group with respect to the IRI group ( p < 0.05 ) .
The TOS and OSI levels , indicating increased oxidative stress , @ @ @ @ @ @ @ with respect to the IRI group ( p < 0.001 ) , but still higher than the control group ( p < 0.001 ) .
In addition to GSH , SOD and Total Thiol levels , TAS levels were also significantly higher in IRI + ASX group in comparison to the IRI group ( p < 0.05 ) .
TNF-α , IL-6 , lipid hydroperoxide , AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group ( p < 0.001 ) .
MPO , IL-6 , TNF-α levels , @ @ @ @ @ @ @ inflammation of the renal tissues , significantly increased in IRI group with respect to the other groups ( p < 0.005 ) .
CONCLUSION : When all the data obtained in our study were evaluated , ASX was determined to prevent renal damage due to renovascular occlusion to a great extent , through complex mechanisms involving antioxidant , anti-inflammatory and antiapopitotic effects .
Biochemical , histological and oxidative stress parameters were improved due to ASX .

BACKGROUND: Various effects of Astaxanthin was shown in the studies including its antioxidant, anti-inflammatory, anti-tumor and immunregulator effects.
OBJECTIVE: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms.
METHODS: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemiareperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were performed for each group.
RESULTS: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to IRI group and close to the level of the control group (p<0.05). Caspase-3 levels of tissue samples were significantly increased in IRI group compared to other groups, but significantly lower in IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p<0.001), but still higher than the control group (p<0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in IRI + ASX group in comparison to the IRI group (p<0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p<0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in IRI group with respect to the other groups (p<0.005).
CONCLUSION: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapopitotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.


greenmedinfo--2020-10-03--Astaxanthin could be useful for treating dry skin caused by decreased AQP3.

Astaxanthin ( 3,3'-dihydroxy-β , β-carotene-4,4'-dione ) is a red lipophilic pigment with strong antioxidant action .
Oral or topical administration of astaxanthin has been reported to improve skin function , including increasing skin moisture .
In this study , we examined the mechanism by which astaxanthin improves skin function byfocusing on the water channel aquaporin-3 ( AQP3 ) , which plays important roles in maintaining skin moisture and function .
When astaxanthin was added to PHK16-0b or HaCaT cells , the mRNA expression level of AQP3 increased significantly in a concentration-dependent manner in both cell lines .
The AQP3protein expression @ @ @ @ @ @ @ astaxanthin was added to HaCaT cells .
Similarly , when astaxanthin was added to 3D human epidermis model EpiSkin , AQP3 expression increased .
Furthermore , when glycerol and astaxanthin were simultaneously added to EpiSkin , glycerol permeability increased significantly compared with that observed for the addition of glycerol alone .
We demonstrated that astaxanthin increases AQP3 expression in the skin and enhances AQP3 activity .
This result suggests that the increased AQP3 expression in the skin is associated with the increase in skin moisture by astaxanthin .
Thus , we consider astaxanthin @ @ @ @ @ @ @ decreased AQP3 due to factors such as diabetes mellitus and aging .

Astaxanthin (3,3'-dihydroxy-β,β-carotene-4,4'-dione) is a red lipophilic pigment with strong antioxidant action. Oral or topical administration of astaxanthin has been reported to improve skin function, including increasing skin moisture. In this study, we examined the mechanism by which astaxanthin improves skin function byfocusing on the water channel aquaporin-3 (AQP3), which plays important roles in maintaining skin moisture and function. When astaxanthin was added to PHK16-0b or HaCaT cells, the mRNA expression level of AQP3 increased significantly in a concentration-dependent manner in both cell lines. The AQP3protein expression level was also confirmed to increase when astaxanthin was added to HaCaT cells. Similarly, when astaxanthin was added to 3D human epidermis model EpiSkin, AQP3 expression increased. Furthermore, when glycerol and astaxanthin were simultaneously added to EpiSkin, glycerol permeability increased significantly compared with that observed for the addition of glycerol alone. We demonstrated that astaxanthin increases AQP3 expression in the skin and enhances AQP3 activity. This result suggests that the increased AQP3 expression in the skin is associated with the increase in skin moisture by astaxanthin. Thus, we consider astaxanthin useful for treating dry skin caused by decreased AQP3 due to factors such as diabetes mellitus and aging.


greenmedinfo--2020-10-03--Astaxanthin prevents lung injury due to hyperoxia and inflammation.

BACKGROUND/AIM : We aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia ( BPD ) induced by hyperoxia and lipopolysaccharide ( LPS ) .
MATERIALS AND METHODS : Forty-two newborn Wistar rats born to spontaneous pregnant rats were divided into three groups : Hyperoxia ( 95 % O2 ) + lipopolysaccharide ( LPS ) group , hyperoxia + LPS + astaxhantin group and control : no treatment group ( 21 % O2 ) .
Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day @ @ @ @ @ @ @ biochemical evaluations including glutathione ( GSH ) , total antioxidant status ( TAS ) , total oxidant status ( TOS ) , lipid hydroperoxide ( LPO ) , 8-hydroxydeoxyguanosine ( 8-OHdG ) , advanced oxidation protein products ( AOPP ) , myeloperoxidase ( MPO ) , total thiol , tumor necrosis factor-alpha ( TNF-α ) , interleukin 1 beta ( IL1β ) and caspase-3 activities were performed .
RESULTS : A better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group ( p < 0.001 ) .
@ @ @ @ @ @ @ of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group , as well as decreased apoptosis ( ELİSA for caspase-3 ) ( p < 0.001 ) .
The biochemical analyses of lung tissues TAS , GSH , Total thiol levels were significantly higher in the astaxanthin treated group compared to hyperoxia + LPS group ( p < 0.05 ) while TOS , AOPP , LPO , 8-OHdG , MPO levels were significantly lower ( p < 0.001 ) .
In addition , unlike the hyperoxia + LPS group , TNF-α and IL-1β levels @ @ @ @ @ @ @ the astaxanthin-treated group ( p < 0.001 ) .
CONCLUSION : Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its antiinflammatory , anti-oxidant , anti-apoptotic properties and to protect the lung from severe destruction .

BACKGROUND/AIM: We aimed to ascertain the effects of astaxanthin on the lungs of rat pups with bronchopulmonary dysplasia (BPD) induced by hyperoxia and lipopolysaccharide (LPS).
MATERIALS AND METHODS: Forty-two newborn Wistar rats born to spontaneous pregnant rats were divided into three groups: Hyperoxia (95% O2) + lipopolysaccharide (LPS) group, hyperoxia + LPS + astaxhantin group and control: no treatment group (21% O2). Pups in the hyperoxia + LPS + astaxanthin group were given 100 mg/kg/day oral astaxanthin from the first day to the fifth day. Histopathologic and biochemical evaluations including glutathione (GSH), total antioxidant status (TAS), total oxidant status (TOS), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), total thiol, tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL1β) and caspase-3 activities were performed.
RESULTS: A better survival rates and weight gain were demonstrated in the hyperoxia + LPS + astaxanthin group (p<0.001). In the histopathologic evaluation, the severity of lung damage was significantly reduced in the hyperoxia+LPS+astaxanthin group, as well as decreased apoptosis (ELİSA for caspase-3) (p<0.001). The biochemical analyses of lung tissues TAS, GSH, Total thiol levels were significantly higher in the astaxanthin treated group compared to hyperoxia + LPS group (p<0.05) while TOS, AOPP, LPO, 8-OHdG, MPO levels were significantly lower (p<0.001). In addition, unlike the hyperoxia + LPS group, TNF-α and IL-1β levels in lung tissue were significantly lower in the astaxanthin-treated group (p<0.001).
CONCLUSION: Astaxanthin was shown to reduce lung damage caused by inflammation and hyperoxia with its antiinflammatory, anti-oxidant, anti-apoptotic properties and to protect the lung from severe destruction.


greenmedinfo--2020-10-03--Kidney-targeted astaxanthin natural antioxidant nanosystem for diabetic nephropathy therapy.

Diabetic nephropathy ( DN ) is a frequent and severe microvascular complication associated with oxidative stress of diabetes mellitus .
@ @ @ @ @ nanosystem , namely AST-GLU-LIP , with preferential renal uptake and bioavailability were prepared and applied @ @ @ @ @ in rats .
Our results of kidney-targeted evaluation showed that glucose-PEG-DSPE ligand modified AST liposomes @ @ @ @ @ overexpressed GLUT1 on the membrane of glomerular mesangial cells and achieved excellent kidney-targeted drug delivery @ @ @ @ @ results of pharmacodynamics and therapeutics in DN rats demonstrated that AST-GLU-LIP could improve the bioavailability @ @ @ @ @ to scavenge redundant ROS induced by oxidative stress .
AST-GLU-LIP could also significantly improve the @ @ @ @ @ the kidney as a therapeutic drug for diabetic nephropathy .

Diabetic nephropathy (DN) is a frequent and severe microvascular complication associated with oxidative stress of diabetes mellitus. A novel astaxanthin-based natural antioxidant nanosystem, namely AST-GLU-LIP, with preferential renal uptake and bioavailability were prepared and applied for treatment of diabetic nephropathy in rats. Our results of kidney-targeted evaluation showed that glucose-PEG-DSPE ligand modified AST liposomes could be specifically transported by overexpressed GLUT1 on the membrane of glomerular mesangial cells and achieved excellent kidney-targeted drug delivery. In addition, the results of pharmacodynamics and therapeutics in DN rats demonstrated that AST-GLU-LIP could improve the bioavailability and antioxidant capacity of AST to scavenge redundant ROS induced by oxidative stress. AST-GLU-LIP could also significantly improve the renal pathological morphology to protect the kidney as a therapeutic drug for diabetic nephropathy.


greenmedinfo--2020-10-03--This model supports the use of astaxanthin for the treatment of cognitive deficits.

Astaxanthin ( Ast ) is an effective neuroprotective and antioxidant compound used to treat Alzheimer 's disease ( AD ) ; however , the underlying in vivo molecular mechanisms remain unknown .
In this study , we report that Ast can activate the mammalian target of rapamycin ( mTOR ) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD .
Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway .
Moreover , mTOR activation perturbed the mitochondrial dynamics , increased the synaptic plasticity after 21 days of treatment with Ast @ @ @ @ @ @ @ the expression of Aβ-degrading enzymes , mitochondrial fusion , and synapse-associated proteins and decreased the expression of mitochondrial fission proteins .
Intraperitoneal injection of the mTOR inhibitor , rapamycin , abolished the effects of Ast .
In conclusion , Ast activates the mTOR pathway , which is necessary for mitochondrial dynamics and synaptic plasticity , leading to improved learning and memory .
Our results support the use of Ast for the treatment of cognitive deficits .
Graphical abstract In summary , Ast ameliorates cognitive deficits via facilitating the mTOR-dependent mitochondrial dynamics and synaptic @ @ @ @ @ @ @ This model supports the use of Ast for the treatment of cognitive deficits .

Astaxanthin (Ast) is an effective neuroprotective and antioxidant compound used to treat Alzheimer's disease (AD); however, the underlying in vivo molecular mechanisms remain unknown. In this study, we report that Ast can activate the mammalian target of rapamycin (mTOR) pathway in the 8-month-old APP/PS1 transgenic mouse model of AD. Our results suggest that Ast could ameliorate the cognitive defects in APP/PS1 mice by activating the mTOR pathway. Moreover, mTOR activation perturbed the mitochondrial dynamics, increased the synaptic plasticity after 21 days of treatment with Ast (10 mg/kg/day), and increased the expression of Aβ-degrading enzymes, mitochondrial fusion, and synapse-associated proteins and decreased the expression of mitochondrial fission proteins. Intraperitoneal injection of the mTOR inhibitor, rapamycin, abolished the effects of Ast. In conclusion, Ast activates the mTOR pathway, which is necessary for mitochondrial dynamics and synaptic plasticity, leading to improved learning and memory. Our results support the use of Ast for the treatment of cognitive deficits. Graphical abstract In summary, Ast ameliorates cognitive deficits via facilitating the mTOR-dependent mitochondrial dynamics and synaptic damage, and reducing Aβ accumulation. This model supports the use of Ast for the treatment of cognitive deficits.


greenmedinfo--2020-10-03--These results suggest that both astaxanthin and adonixanthin have potential as treatments for gliobl

Several antitumour drugs have been isolated from natural products and many clinical trials are underway to evaluate their potential .
@ @ @ @ @ about the antitumour effects of astaxanthin against several tumours but no studies into its effects @ @ @ @ @ a red pigment found in crustaceans and fish and is also synthesized in ; adonixanthin @ @ @ @ @ astaxanthin .
It is known that both astaxanthin and adonixanthin possess radical scavenging activity and @ @ @ @ @ on several damages .
In this study , we clarified the antitumour effects of astaxanthin @ @ @ @ @ .
Specifically , astaxanthin and adonixanthin showed an ability to suppress cell proliferation and migration @ @ @ @ @ cells .
Furthermore , these compounds were confirmed to transfer to the brain in a @ @ @ @ @ murine orthotopic glioblastoma model , glioblastoma progression was suppressed by the oral administration of astaxanthin @ @ @ @ @ 30 mg/kg , respectively , for 10 days .
These results suggest that both astaxanthin @ @ @ @ @ treatments for glioblastoma .

Several antitumour drugs have been isolated from natural products and many clinical trials are underway to evaluate their potential. There have been numerous reports about the antitumour effects of astaxanthin against several tumours but no studies into its effects against glioblastoma. Astaxanthin is a red pigment found in crustaceans and fish and is also synthesized in; adonixanthin is an intermediate product of astaxanthin. It is known that both astaxanthin and adonixanthin possess radical scavenging activity and can confer a protective effect on several damages. In this study, we clarified the antitumour effects of astaxanthin and adonixanthin using glioblastoma models. Specifically, astaxanthin and adonixanthin showed an ability to suppress cell proliferation and migration in three types of glioblastoma cells. Furthermore, these compounds were confirmed to transfer to the brain in a murine model. In the murine orthotopic glioblastoma model, glioblastoma progression was suppressed by the oral administration of astaxanthin and adonixanthin at 10 and 30 mg/kg, respectively, for 10 days. These results suggest that both astaxanthin and adonixanthin have potential as treatments for glioblastoma.


greenmedinfo--2020-10-03--Astaxanthin inhibits p70 S6 kinase 1 activity to sensitize insulin signaling.

Astaxanthin ( AST ) is a carotenoid with therapeutic values on hyperglycemia and diabetic complications .
The mechanisms of action of AST remain incompletely understood .
p70 S6 kinase 1 ( S6K1 ) is a serine/threonine kinase that phosphorylates insulin receptor substrate 1 ( IRS-1 ) and desensitizes the insulin receptor ( IR ) .
Our present study aims to determine if AST improves glucose metabolisms by targeting S6K1 .
Western blot analysis revealed that AST inhibited the phosphorylation of two S6K1 substrates , S6and IRS-1 , but enhanced the phosphorylation of AKT , AKT , and S6K1by feedback activation @ @ @ @ @ @ @ in 3T3-L1 adipocytes and L6 myotubes .
In vitro kinase assays revealed that AST inhibited S6K1 activity with an ICvalue of approximately 13.8μM .
AST increased insulin-induced IR tyrosine phosphorylation and IRS-1 binding to the p85 subunit of PI-3 kinase .
Confocal microscopy revealed that AST increased the translocation of the glucose transporter 4 ( GLUT4 ) to the plasma membrane in L6 cells .
Glucose uptake assays using a fluorescent dye , 2-NBDG ( 2 -- ( Nitrobenz-2-oxa-1,3-diazol-4-yl ) amino ) -2-deoxyglucose ) , revealed that AST increased glucose uptake in 3T3-L1 @ @ @ @ @ @ @ conditions .
Our study identifies S6K1 as a previously unrecognized molecular target of AST and provides novel insights into the mechanisms of action of AST on IR sensitization .

Astaxanthin (AST) is a carotenoid with therapeutic values on hyperglycemia and diabetic complications. The mechanisms of action of AST remain incompletely understood. p70 S6 kinase 1 (S6K1) is a serine/threonine kinase that phosphorylates insulin receptor substrate 1 (IRS-1)and desensitizes the insulin receptor (IR). Our present study aims to determine if AST improves glucose metabolisms by targeting S6K1. Western blot analysis revealed that AST inhibited the phosphorylation of two S6K1 substrates, S6and IRS-1, but enhanced the phosphorylation of AKT, AKT, and S6K1by feedback activation of the phosphatidylinositol-3 (PI-3) kinase in 3T3-L1 adipocytes and L6 myotubes. In vitro kinase assays revealed that AST inhibited S6K1 activity with an ICvalue of approximately 13.8μM. AST increased insulin-induced IR tyrosine phosphorylation and IRS-1 binding to the p85 subunit of PI-3 kinase. Confocal microscopy revealed that AST increased the translocation of the glucose transporter 4 (GLUT4) to the plasma membrane in L6 cells. Glucose uptake assays using a fluorescent dye, 2-NBDG (2--(Nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose), revealed that AST increased glucose uptake in 3T3-L1 adipocytes and L6 myotubes under insulin resistance conditions. Our study identifies S6K1 as a previously unrecognized molecular target of AST and provides novel insights into the mechanisms of action of AST on IR sensitization.


greenmedinfo--2020-10-03--Astragaloside IV treatment ameliorated the severity of diabetic nephropathy.

Background : Diabetic nephropathy ( DN ) is one of the leading causes of end-stage kidney disease .
Recently , there is no specific drug available to block the kidney damage .
Astragaloside IV ( AS-IV ) is a major active component of ( Fisch ) Bge and has been demonstrated to benefit the kidney functions .
This study explores the potential pharmacological action of AS-IV in DN of rats .
Methods : Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes .
The diabetic rats were randomized and treated with vehicle or AS-IV @ @ @ @ @ @ @ for 12 weeks as the DN or AS-IV group , respectively .
The normal control rats were fed with normal chow and injected with vehicles ( = 8 per group ) .
These rats were monitored for diabetes- and kidney function-related measures .
The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR .
The levels of advanced glycation end products ( AGEs ) , IL-1 , and IL-18 in the serum samples and kidney tissues were quantified by ELISA .
The levels of collagen @ @ @ @ @ @ @ FN ) expression in kidney tissues were examined by immunohistochemistry and Western blot .
Results : In comparison with the DN group , AS-IV treatment significantly reduced blood glucose levels , food and water consumption , 24 h urine , renal index values , 24 h urine total proteins , blood urea nitrogen ( BUN ) levels , and creatinine clearance rates ( CCR ) , accompanied by minimizing the DN-induced early kidney damages , fibrosis , and microstructural changes .
Furthermore , AS-IV treatment significantly modulated the DN-altered gene transcription profiles in @ @ @ @ @ @ @ inflammation-related genes , including the nucleotide-binding oligomerization domain-like receptor signaling , which was validated by quantitative RT-PCR .
AS-IV treatment significantly decreased the levels of serum and kidney AGEs , IL-1 , and IL-18 expression and fibrosis indexes in the kidney of rats .
Conclusion : AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats .

Background: Diabetic nephropathy (DN) is one of the leading causes of end-stage kidney disease. Recently, there is no specific drug available to block the kidney damage. Astragaloside IV (AS-IV) is a major active component of(Fisch) Bge and has been demonstrated to benefit the kidney functions. This study explores the potential pharmacological action of AS-IV in DN of rats.
Methods: Male Sprague-Dawley rats were fed with high-fat diet and injected with streptozotocin to induce diabetes. The diabetic rats were randomized and treated with vehicle or AS-IV (80 mg/kg) daily by gavage for 12 weeks as the DN or AS-IV group, respectively. The normal control rats were fed with normal chow and injected with vehicles (= 8 per group). These rats were monitored for diabetes- and kidney function-related measures. The expression profiles of gene mRNA transcripts in the kidney tissues were analyzed by RNA-seq and quantitative RT-PCR. The levels of advanced glycation end products (AGEs), IL-1, and IL-18 in the serum samples and kidney tissues were quantified by ELISA. The levels of collagen IV (COL-4) and fibronectin (FN) expression in kidney tissues were examined by immunohistochemistry and Western blot.
Results: In comparison with the DN group, AS-IV treatment significantly reduced blood glucose levels, food and water consumption, 24 h urine, renal index values, 24 h urine total proteins, blood urea nitrogen (BUN) levels, and creatinine clearance rates (CCR), accompanied by minimizing the DN-induced early kidney damages, fibrosis, and microstructural changes. Furthermore, AS-IV treatment significantly modulated the DN-altered gene transcription profiles in the kidney of rats, particularly for inflammation-related genes, including the nucleotide-binding oligomerization domain-like receptor signaling, which was validated by quantitative RT-PCR. AS-IV treatment significantly decreased the levels of serum and kidney AGEs,IL-1, and IL-18 expression and fibrosis indexes in the kidney of rats.
Conclusion: AS-IV treatment ameliorated the severity of DN by inhibiting inflammation-related gene expression in the kidney of rats.


greenmedinfo--2020-10-03--These data suggested that astragaloside Ⅳ can effectively reduce radiation-induced apoptosis of brai

These data suggested that astragaloside Ⅳ can effectively reduce radiation-induced apoptosis of brain cells.

With multiple targets and low cytotoxicity , natural medicines can be used as potential neuroprotective agents .
The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure , and ultimately leads to abnormal changes in neurogenesis , differentiation , and apoptosis .
AstragalosideⅣ ( AS-Ⅳ ) , one of the main active constituents of astragalus , is known for its antioxidant , antihypertensive , antidiabetic , anti-infarction , anti-inflammatory , anti-apoptotic and wound healing , angiogenesis , and other protective effects .
In this study , the mechanism of @ @ @ @ @ @ @ in vitro and in vivo was explored by radiation modeling , which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products .
In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice , the paper constructed a radiation-induced brain cell apoptosis model , using TUNEL staining , flow cytometry , Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis .
The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group @ @ @ @ @ @ @ Western blotting indicated that the expression levels of p-JNK , p-p38 , p53 , Caspase-9 and Caspase-3 protein , and the ratio of Bax to Bcl-2 in radiation group were significantly increased .
There was no significant difference in the expression levels of JNK and p38 .
After AS-IV treatment , the apoptosis was reduced and the expression of apoptosis related proteins was changed .
These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells , and its mechanism may be related to the phosphorylation regulation of JNK-p38 .

With multiple targets and low cytotoxicity, natural medicines can be used as potential neuroprotective agents. The increase in oxidative stress levels and inflammatory responses in the brain caused by radiation affects cognitive function and neuronal structure, and ultimately leads to abnormal changes in neurogenesis, differentiation, and apoptosis. AstragalosideⅣ (AS-Ⅳ), one of the main active constituents of astragalus, is known for its antioxidant, antihypertensive, antidiabetic, anti-infarction, anti-inflammatory, anti-apoptotic and wound healing, angiogenesis, and other protective effects. In this study, the mechanism of AS-IV against radiation-induced apoptosis of brain cells in vitro and in vivo was explored by radiation modeling, which provided a theoretical basis for the development of anti-radiation Chinese herbal active molecules and brain health products. In order to study the protective mechanism of AS-IV on radiation-induced brain cell apoptosis in mice, the paper constructed a radiation-induced brain cell apoptosis model, using TUNEL staining, flow cytometry, Western blotting to analyze AS-IV resistance mechanism to radiation-induced brain cell apoptosis. The results of TUNEL staining and flow cytometry showed that the apoptosis rate of radiation group was significantly increased. The results of Western blotting indicated that the expression levels of p-JNK, p-p38, p53, Caspase-9 and Caspase-3 protein, and the ratio of Bax to Bcl-2 in radiation group were significantly increased. There was no significant difference in the expression levels of JNK and p38. After AS-IV treatment, the apoptosis was reduced and the expression of apoptosis related proteins was changed. These data suggested that AS-IV can effectively reduce radiation-induced apoptosis of brain cells, and its mechanism may be related to the phosphorylation regulation of JNK-p38.