greenmedinfo--2020-09-02--Antiproliferative activity of Citrus juices and HPLC evaluation of their flavonoid composition.

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greenmedinfo--2020-09-02--Protective effects of oridonin on the sepsis in mice.

This study aimed to investigate the protective effects of oridonin ( ORI ) on cecal ligation and puncture ( CLP @ @ @ @ @ .
Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to @ @ @ @ @ , CLP group , or CLP plus ORI group .
In the CLP group and @ @ @ @ @ induced , and intraperitoneal injection of normal saline and oridonin ( 100 μg/kg ) was @ @ @ @ @ survival rate was determined within the following 7 days .
The blood , liver , @ @ @ @ @ 24 hours after injury .
Hematoxylin-eosin staining of the lung , detection of lung wet-to-dry @ @ @ @ @ ( tumor necrosis factor [ TNF ] -α and interleukin [ IL ] -6 ) @ @ @ @ @ and blood bacterial clearance were conducted to evaluate the therapeutic efficacy .
Results showed that @ @ @ @ @ lung wet-to-dry ratio , decreased serum TNF-α and IL-6 , and improved liver pathology compared @ @ @ @ @ p

This study aimed to investigate the protective effects of oridonin (ORI) on cecal ligation and puncture (CLP)-induced sepsis in mice. Male C57BL/6 mice weighing 22-30 g and aged 8-10 weeks were randomly assigned to three groups: Sham group, CLP group, or CLP plus ORI group. In the CLP group and ORI group, CLP was induced, and intraperitoneal injection of normal saline and oridonin (100 μg/kg) was conducted, respectively. The survival rate was determined within the following 7 days. The blood, liver, and lung were collected at 24 hours after injury. Hematoxylin-eosin staining of the lung, detection of lung wet-to-dry ratio, and serum cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6), and examination of intraperitoneal and blood bacterial clearance were conducted to evaluate the therapeutic efficacy. Results showed that ORI treatment significantly reduced the lung wet-to-dry ratio, decreased serum TNF-α and IL-6, and improved liver pathology compared with the CLP group (p < 0.05). Moreover, the intraperitoneal and blood bacterial clearance increased markedly after ORI treatment (p < 0.05). The 7-day survival rate in the ORI group was also dramatically higher than in the CLP group (p < 0.05). Our findings indicate that ORI can attenuate liver and lung injuries and elevate bacterial clearance to increase the survival rate of sepsis mice.


greenmedinfo--2020-09-02--Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamou

Combined oridonin with cetuximab treatment shows synergistic anticancer effects on laryngeal squamous cell carcinoma.

Epidermal growth factor receptor ( EGFR ) , a transmembrane glycoprotein , is expressed at high levels in a large proportion of laryngeal squamous cell carcinoma ( LSCC ) .
Cetuximab ( Cet ) , an anti-EGFR monoclonal antibody , has limited clinical outcome for patients with head and neck squamous cell carcinoma .
Our previous studies showed that oridonin ( ORI ) , a natural and safe kaurene diterpenoid isolated from Rabdosia rubescens , inhibited cell growth in HEp-2 cells through inhibition of EGFR phosphorylation .
The aim of the present study was to determine whether ORI could improve @ @ @ @ @ @ @ .
We observed that the combination with Cet and ORI synergistically inhibited cell growth associated with Fas-mediated apoptosis and G2/M phase arrest in two LSCC cell lines ( HEp-2 and Tu212 cells ) .
Moreover , combination treatment caused cell death associated with suppression of p-EGFR and activation of reactive oxygen species ( ROS ) -mediated JNK pathway .
In nude mice bearing HEp-2 xenografts , ORI plus Cet caused a significant tumor regression through induction of apoptosis and inhibition of proliferation with no side-effect .
Together , our findings suggest that the @ @ @ @ @ @ @ potential to enhance tumor responses and may significantly improve therapeutic outcomes in LSCC .

Epidermal growth factor receptor (EGFR), a transmembrane glycoprotein, is expressed at high levels in a large proportion of laryngeal squamous cell carcinoma (LSCC). Cetuximab (Cet), an anti-EGFR monoclonal antibody, has limited clinical outcome for patients with head and neck squamous cell carcinoma. Our previous studies showed that oridonin (ORI), a natural and safe kaurene diterpenoid isolated from Rabdosia rubescens, inhibited cell growth in HEp-2 cells through inhibition of EGFR phosphorylation. The aim of the present study was to determine whether ORI could improve the anticancer efficacy of Cet on LSCC. We observed that the combination with Cet and ORI synergistically inhibited cell growth associated with Fas-mediated apoptosis and G2/M phase arrest in two LSCC cell lines (HEp-2 and Tu212 cells). Moreover, combination treatment caused cell death associated with suppression of p-EGFR and activation of reactive oxygen species (ROS)-mediated JNK pathway. In nude mice bearing HEp-2 xenografts, ORI plus Cet caused a significant tumor regression through induction of apoptosis and inhibition of proliferation with no side-effect. Together, our findings suggest that the combination of ORI and Cet has the potential to enhance tumor responses and may significantly improve therapeutic outcomes in LSCC.


greenmedinfo--2020-09-02--Oridonin inhibition and miR‑200b‑3p/ZEB1 axis in human pancreatic cancer.

The relationship among oridonin , miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition ( EMT ) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer .
BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array .
The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted .
BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p , those cells were used for western blot assay , Transwell assay , ELISA , immunofluorescence staining @ @ @ @ @ @ @ assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer .
We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner .
miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells .
ZEB1 was a target gene formiR-200b-3p .
Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells .
miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1 , N-cadherin and fibronectin but not increase the expression of E-cadherin , while the cell adhesion @ @ @ @ @ @ @ oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control .
In summary , the results demonstrate that miR‑200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro bytargeted ZEB1 .
In vitro , oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells , but not though type III EMT by miR-200-3p/ZEB1 axis , and may be related to type Ⅱ EMT , tumor microenvironment or altering the cytoskeleton .
In vivo , @ @ @ @ @ @ @ nude mouse model though inhibiting EMT .

The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR‑200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice andimmunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene formiR-200b-3p. Oridonin or overexpression of miR‑200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR‑200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro bytargeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type Ⅱ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.


greenmedinfo--2020-09-02--Oridonin promotes G2/M arrest in A549 cells by facilitating ATM activation.

Previous studies have demonstrated that oridonin , a tetracyclic diterpenoid compound extracted from Rabdosia rubescens , inhibits proliferation and induces @ @ @ @ @ lines .
However , the mechanism by which oridonin inhibits the cell cycle remains poorly @ @ @ @ @ study , possible mechanisms by which oridonin affects cell cycle progression were explored in A549 @ @ @ @ @ cytometry analysis indicated that oridonin inhibited the proliferation of A549 cells by inducing G2/M cell @ @ @ @ @ manner .
Western blot analysis revealed that in oridonin treated cells , phosphorylated ( p‑ @ @ @ @ @ S1981 ) , p‑checkpoint kinase 2 ( CHK2 ) ( T68 ) , p‑p53 , @ @ @ @ @ member X protein levels were visibly increased , indicating that oridonin promoted G2/M arrest in @ @ @ @ @ pathway .
This data suggests that oridonin promotes G2/M arrest in A549 cells by facilitating @ @ @ @ @ likely a common mechanism in other tumor cell types when using this drug for cancer @ @

Previous studies have demonstrated that oridonin, a tetracyclic diterpenoid compound extracted from Rabdosia rubescens, inhibits proliferation and induces apoptosis in several tumor cell lines. However, the mechanism by which oridonin inhibits the cell cycle remains poorly understood. In the present study, possible mechanisms by which oridonin affects cell cycle progression were explored in A549 lung cancer cells. Flow cytometry analysis indicated that oridonin inhibited the proliferation of A549 cells by inducing G2/M cell cycle arrest in a dose‑dependent manner. Western blot analysis revealed that in oridonin treated cells, phosphorylated (p‑)ATM serine/threonine kinase (S1981), p‑checkpoint kinase 2 (CHK2) (T68), p‑p53, and phosphorylated H2A histone family member X protein levels were visibly increased, indicating that oridonin promoted G2/M arrest in A549 cells through the ATM‑p53‑CHK2 pathway. This data suggests that oridonin promotes G2/M arrest in A549 cells by facilitating ATM activation, which is likely a common mechanism in other tumor cell types when using this drug for cancer treatment.


greenmedinfo--2020-09-02--Greenmedinfo Deleted from Instagram and Linkedin (Facebook Next?) Has The Great Social Media Purge o

Greenmedinfo Deleted from Instagram and Linkedin (Facebook Next?) Has The Great Social Media Purge of 2020 Begun?

In a sudden move without explanation , Instagram deletes GreenMedInfo.com 's account , cutting off 90,000 subscribers ...
But this is likely only the beginning of a great 'Social Media Purge ' anticipated to unfold as part of the highly engineered response to COVID-19 SPECIAL ANNOUNCEMENT : JOIN TONIGHT 'S SPECIAL LIVESTREAM TO DISCUSS THE DEPLATFORMING OF GREENMEDINFO.COM AND THE ANTICIPATED GREAT SOCIAL MEDIA PURGE OF 2020 .
Bookmark or visit this link .
Today , Instagram followed through with their previous threats from July 8th and July 30th to delete the account of Greenmedinfo.com , ostensibly for posting `` @ @ @ @ @ @ @ this post by Ron Paul : Today 's action by Instagram was carried out without any explanation .
The only statement Instagram provided was `` Your Account Has Been Disabled . ''
The GreenMedInfo.com account had over 90,000 followers at the time .
Instagram is a social networking service owned by Facebook .
And recently , AVAAZ published a report created by Newsguard suggesting that Greenmedinfo.com should be censored further on Facebook for spreading health misinformation ; a report amplified by the NY Times in a recent opinion piece .
I cover this @ @ @ @ @ @ @ can view in this video .
Not Our First De-Platforming Rodeo Back in December of 2018 , Pinterest removed our account for posting on natural health and vaccine-related topics .
In May of 2019 , Mailchimp deplatformed us , preventing us from sending emails .
It was later found out that they are CDC foundation funding partners , explaining why they would egregiously violate our freedom of speech on health matters .
In June 2019 , Google enacted their `` Great Digital Book Burning Event , '' removing natural health organizations , such @ @ @ @ @ @ @ , from organic search results .
Last month , after over a decade of using the platform and with over 7,000 professional connections , LinkedIn removed my account , and my ability to access our Greenmedinfo.com group there .
Since the COVID crisis emerged , I have been openly critical of the Gates foundation there and was interested to learn that Microsoft bought LinkedIn in 2018 for 26.2 billion dollars .
You can view the timeline of our deplatforming , along with the specific dates and our reporting on each event , here @ @ @ @ @ @ @ the fact that our Facebook page has close to 550,000 followers , and yet our average post reach only ends up in the feeds of less than .05 % , Facebook has already effectively `` boiled the frog '' of our penetrance there , and has architected what could be described as a de facto deletion of our page .
That said , even with the algorithmic shadow banning and de-boosting of all our posts , the AVAAZ/Newsguard report still attributed a huge impact of our reach there in their highly misleading report @ @ @ @ @ @ @ Major Threat to Public Health .
Similarly , the New York Times identified our brand 's Facebook reach as a `` super spreader or health misinformation , '' even though technically our now-deleted Instagram account received 10x more engagement .
Whether correct or not about our reach , the reality is that our platform 's social media extensions have been targeted for deletion , and this does not bode well for freedom of speech , nor the future of dialogue around health matters with massive sociopolitical implications for the world .
In a @ @ @ @ @ @ @ opinion or belief , or exercising your choice on matters of health ( e.g .
to vaccinate or not ) , can result in fines , arrest , loss of a job , or forced isolation or separation of family members , access to non-industry-supported health information ( like that in our database of over 60,000 abstracts from peer-reviewed journals ) may indeed change the course of human history .
We believe that this censorship wave is extremely relevant to the health and even political freedom of this entire country .
If you @ @ @ @ @ @ @ the free flow of information , you are not only violating our Constitutional rights and right to the medical ethical principle of informed consent , but you are moving down the well-trodden path towards atrocities related to dehumanization and even genocide .
Interestingly , I wrote about this only months before the COVID crisis struck the world in an article titled , `` Vaccine Extremism , Hate Speech , and the Well-Beaten Path Towards Genocide . ''
It behooves us all to take into careful consideration the implications of silencing voices like ours @ @ @ @ @ @ @ as a whole .
When only one narrative is permitted dominance , as we are seeing with the increasingly cult-like adherence to conventional medical and governmental Covid mandates , all available information is propaganda that serves the few and harms the many.. Heinrich Heine warned us about this when he said , The good news here is that we anticipated these attempts to silence us and the millions like us who share our views and believe they actually reflect a positive development : namely , the powers that be realize that they ca @ @ @ @ @ @ @ around the world who see through this biosecurity agenda .
We already have close to 16,000 subscribers to our relatively new Telegram channel , where you receive 100 % of our content , in real time .
We also have a thriving online community via our Greenmedinfo.com newsletter , which has survived censorship multiple times , and has grown in leaps and bounds as a result of these attempts .
We also welcome members and donations to support this 100 % user-supported platform .
Finally , join the www.Standforhealthfreedom.com community , a non-profit @ @ @ @ @ @ @ to empower you to make an impact in the name of parental rights , bodily self-sovereignty , informed consent , and health freedom as a whole .
And please do share this article with others to help break through the oppressive algorithmic shackles they 're trying to lay upon us !
Join Tonight 's Livestream , 5 PM EST , to discuss the Deplatforming , and the Opportunity It Represents for The Health Freedom Movement .
Visit or bookmark the link to the livestream here .

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
In a sudden move without explanation, Instagram deletes GreenMedInfo.com's account, cutting off 90,000 subscribers...But this is likely only the beginning of a great 'Social Media Purge' anticipated to unfold as part of the highly engineered response to COVID-19
SPECIAL ANNOUNCEMENT: WATCH OUR SEPT. 3RD LIVESTREAM BELOW ON THE DEPLATFORMING OF GREENMEDINFO.COM AND THE ANTICIPATED GREAT SOCIAL MEDIA PURGE OF 2020.
Today, Instagram followed through with their previous threats from July 8th and July 30th to delete the account of Greenmedinfo.com, ostensibly for posting "harmful false information," such as this post by Ron Paul:
Today's action by Instagram was carried out without any explanation. The only statement Instagram provided was "Your Account Has Been Disabled." The GreenMedInfo.com account had over 90,000 followers at the time.
First Instagram, Facebook Next?
Instagram is a social networking service owned by Facebook. And recently, AVAAZ published a report created by Newsguard suggesting that Greenmedinfo.com should be censored further on Facebook for spreading health misinformation; a report amplified by the NY Times in a recent opinion piece. I cover this development in a recent livestream recording you can view in this video.
Not Our First De-Platforming Rodeo
Back in December of 2018, Pinterest removed our account for posting on natural health and vaccine-related topics. In May of 2019, Mailchimp deplatformed us, preventing us from sending emails. It was later found out that they are CDC foundation funding partners, explaining why they would egregiously violate our freedom of speech on health matters. In June 2019, Google enacted their "Great Digital Book Burning Event," removing natural health organizations, such as Greenmedinfo.com, Mercola.com, and Kellybroganmd.com, from organic search results. Last month, after over a decade of using the platform and with over 7,000 professional connections, LinkedIn removed my account, and my ability to access our Greenmedinfo.com group there. Since the COVID crisis emerged, I have been openly critical of the Gates foundation there and was interested to learn that Microsoft bought LinkedIn in 2018 for 26.2 billion dollars. You can view the timeline of our deplatforming, along with the specific dates and our reporting on each event, here.
Will Facebook Be Next?
Given the fact that our Facebook page has close to 550,000 followers, and yet our average post reach only ends up in the feeds of less than .05%, Facebook has already effectively "boiled the frog" of our penetrance there, and has architected what could be described as a de facto deletion of our page. That said, even with the algorithmic shadow banning and de-boosting of all our posts, the AVAAZ/Newsguard report still attributed a huge impact of our reach there in their highly misleading report titled, Facebook's Algorithm: A Major Threat to Public Health. Similarly, the New York Times identified our brand's Facebook reach as a "super spreader or health misinformation," even though technically our now-deleted Instagram account received 10x more engagement.
Whether correct or not about our reach, the reality is that our platform's social media extensions have been targeted for deletion, and this does not bode well for freedom of speech, nor the future of dialogue around health matters with massive sociopolitical implications for the world. In a day and age where having a medical opinion or belief, or exercising your choice on matters of health (e.g. to vaccinate or not), can result in fines, arrest, loss of a job, or forced isolation or separation of family members, access to non-industry-supported health information (like that in our database of over 60,000 abstracts from peer-reviewed journals) may indeed change the course of human history.
We believe that this censorship wave is extremely relevant to the health and even political freedom of this entire country. If you inhibit free speech, or access to the free flow of information, you are not only violating our Constitutional rights and right to the medical ethical principle of informed consent, but you are moving down the well-trodden path towards atrocities related to dehumanization and even genocide. Interestingly, I wrote about this only months before the COVID crisis struck the world in an article titled, "Vaccine Extremism, Hate Speech, and the Well-Beaten Path Towards Genocide."
It behooves us all to take into careful consideration the implications of silencing voices like ours from social media, and the internet as a whole. When only one narrative is permitted dominance, as we are seeing with the increasingly cult-like adherence to conventional medical and governmental Covid mandates, all available information is propaganda that serves the few and harms the many.. Heinrich Heine warned us about this when he said,
"Wherever they burn books, in the end will also burn human beings."
The Call to Action
The good news here is that we anticipated these attempts to silence us and the millions like us who share our views and believe they actually reflect a positive development: namely, the powers that be realize that they can't simply ignore the increasingly awakened populations around the world who see through this biosecurity agenda. We already have close to 16,000 subscribers to our relatively new Telegram channel, where you receive 100% of our content, in real time. We also have a thriving online community via our Greenmedinfo.com newsletter, which has survived censorship multiple times, and has grown in leaps and bounds as a result of these attempts. We also welcome members and donations to support this 100% user-supported platform. Finally, join the www.Standforhealthfreedom.com community, a non-profit which exists to empower you with actions to empower you to make an impact in the name of parental rights, bodily self-sovereignty, informed consent, and health freedom as a whole. And please do share this article with others to help break through the oppressive algorithmic shackles they're trying to lay upon us!


greenmedinfo--2020-09-02--Oridonin triggers chaperon-mediated proteasomal degradation of BCR-ABL in leukemia.

Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be @ @ @ @ @ Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of @ @ @ @ @ direct cellular targets and underlying mechanisms remain unclear .
Here we report that oridonin depletes @ @ @ @ @ in leukemia .
Mechanistically , oridonin poses oxidative stress in cancer cells and directly binds @ @ @ @ @ leading to the activation of this master regulator of the chaperone system .
The resulting @ @ @ @ @ proteins and the enhanced binding to CHIP E3 ligase hence target BCR-ABL for ubiquitin-proteasome degradation @ @ @ @ @ forms of BCR-ABL can be efficiently degraded by oridonin , supporting its efficacy observed in @ @ @ @ @ mouse tumor xenograft assays with either imatinib-sensitive or -resistant cells .
Collectively , our results @ @ @ @ @ which oridonin induces rapid degradation of BCR-ABL as well as a novel pharmaceutical activator of @ @ @ @ @ treatment for leukemia .

Inducing degradation of oncoproteins by small molecule compounds has the potential to avoid drug resistance and therefore deserves to be exploited for new therapies. Oridonin is a natural compound with promising antitumor efficacy that can trigger the degradation of oncoproteins; however, the direct cellular targets and underlying mechanisms remain unclear. Here we report that oridonin depletes BCR-ABL through chaperon-mediated proteasomal degradation in leukemia. Mechanistically, oridonin poses oxidative stress in cancer cells and directly binds to cysteines of HSF1, leading to the activation of this master regulator of the chaperone system. The resulting induction of HSP70 and ubiquitin proteins and the enhanced binding to CHIP E3 ligase hence target BCR-ABL for ubiquitin-proteasome degradation. Both wild-type and mutant forms of BCR-ABL can be efficiently degraded by oridonin, supporting its efficacy observed in cultured cells as well as mouse tumor xenograft assays with either imatinib-sensitive or -resistant cells. Collectively, our results identify a novel mechanism by which oridonin induces rapid degradation of BCR-ABL as well as a novel pharmaceutical activator of HSF1 that represents a promising treatment for leukemia.


greenmedinfo--2020-09-03--Antitumor activity of Moringa oleifera flower trypsin inhibitor in sarcoma 180-bearing mice.

The plant Moringa oleifera is used as food and medicine .
M. oleifera flowers are source of protein , fiber , and antioxidants , and are used to treat inflammation and tumors .
This work evaluated the antitumor activity of the M. oleifera flower trypsin inhibitor ( MoFTI ) in sarcoma 180-bearing mice .
Swiss female mice were inoculated with sarcoma 180 cells .
Seven days later , the animals were treated intraperitoneally for 1 week with daily doses of PBS ( control ) or MoFTI ( 15 or 30 mg/kg ) .
For toxicity assessment , water and food @ @ @ @ @ @ @ histological alterations , and blood hematological and biochemical parameters were measured .
Treatment with MoFTI caused pronounced reduction ( 90.1 % -97.9 % ) in tumor weight .
The tumors of treated animals had a reduced number of secondary vessels and lower gauge of the primary vessels compared to the control .
No significant changes were observed in water and food consumption or inbody and organ weights .
Histopathological analysis did not indicate damage to the liver , kidneys , and spleen .
In conclusion , MoFTI showed antitumor potential , with no @ @ @ @ @

The plant Moringa oleifera is used as food and medicine. M. oleifera flowers are source of protein, fiber, and antioxidants, and are used to treat inflammation and tumors. This work evaluated the antitumor activity of the M. oleifera flower trypsin inhibitor (MoFTI) in sarcoma 180-bearing mice. Swiss female mice were inoculated with sarcoma 180 cells. Seven days later, the animals were treated intraperitoneally for 1 week with daily doses of PBS (control) or MoFTI (15 or 30 mg/kg). For toxicity assessment, water and food consumption, body and organ weights, histological alterations, and blood hematological and biochemical parameters were measured. Treatment with MoFTI caused pronounced reduction (90.1%-97.9%) in tumor weight. The tumors of treated animals had a reduced number of secondary vessels and lower gauge of the primary vessels compared to the control. No significant changes were observed in water and food consumption or inbody and organ weights. Histopathological analysis did not indicate damage to the liver, kidneys, and spleen. In conclusion, MoFTI showed antitumor potential, with no clear evidence of toxicity.


greenmedinfo--2020-09-03--Bactericidal and in vitro cytotoxicity of Moringa oleifera seed extract.

In the current study , we present the correlation between the capability of laser-induced breakdown spectroscopy ( LIBS ) to monitor the elemental compositions of plants and their biological effects .
The selected plant , , is known to harbor various minerals and vitamins useful for human health and is a potential source for pharmaceutical interventions .
From this standpoint , we assessed the antibacterial and in vitro cytotoxicity of the bioactive components present inseed ( MOS ) extract .
Detailed elemental analyses of pellets of MOSs were performed via LIBS .
Furthermore , the LIBS outcome was validated using @ @ @ @ @ @ @ The LIBS signal was recorded , and the presence of the essential elements ( Na , Ca , Se , K , Mg , Zn , P , S , Fe and Mn ) in the MOSs were examined .
The bactericidal efficacy of the alcoholic MOS extract was examined againstandby agar well diffusion ( AWD ) assays and scanning electron microscopy ( SEM ) , which depicted greater inhibition against Gram-positive bacteria .
The validity and DNA nuclear morphology of human colorectal carcinoma cells ( HCT-116 ) cells were evaluated via an @ @ @ @ @ @ @ MTT assay results manifested a profoundly inhibitory action of MOS extract on HCT116 cell growth .
Additionally , MOS extracts produced inhibitory action in colon cancer cells ( HCT-116 ) , whereas no inhibitory action was seen using the same concentrations of MOS extract on HEK-293 cells ( non-cancerous cells ) , suggesting that MOS extracts could be non-cytotoxic to normal cells .
The antibacterial and anticancer potency of these MOS extracts could be due to the presence of various bioactive chemical complexes , such as ethyl ester and D-allose and hexadecenoic , @ @ @ @ @ @ @ an ideal candidate for pharmaceutical research and applications .

In the current study, we present the correlation between the capability of laser-induced breakdown spectroscopy (LIBS) to monitor the elemental compositions of plants and their biological effects. The selected plant,, is known to harbor various minerals and vitamins useful for human health and is a potential source for pharmaceutical interventions. From this standpoint, we assessed the antibacterial and in vitro cytotoxicity of the bioactive components present inseed (MOS) extract. Detailed elemental analyses of pellets of MOSs were performed via LIBS. Furthermore, the LIBS outcome was validated using gas chromatography-mass spectrometry (GC-MS). The LIBS signal was recorded, and the presence of the essential elements (Na, Ca, Se, K, Mg, Zn, P, S, Fe and Mn) in the MOSs were examined. The bactericidal efficacy of the alcoholic MOS extract was examined againstandby agar well diffusion (AWD) assays and scanning electron microscopy (SEM), which depicted greater inhibition against Gram-positive bacteria. The validity and DNA nuclear morphology of human colorectal carcinoma cells (HCT-116) cells were evaluated via an MTT assay and DAPI staining. The MTT assay results manifested a profoundly inhibitory action of MOS extract on HCT116 cell growth. Additionally, MOS extracts produced inhibitory action in colon cancer cells (HCT-116), whereas no inhibitory action was seen using the same concentrations of MOS extract on HEK-293 cells (non-cancerous cells), suggesting that MOS extracts could be non-cytotoxic to normal cells. The antibacterial and anticancer potency of these MOS extracts could be due to the presence of various bioactive chemical complexes, such as ethyl ester and D-allose and hexadecenoic, oleic and palmitic acids, making them an ideal candidate for pharmaceutical research and applications.


greenmedinfo--2020-09-03--A trypsin inhibitor from Moringa oleifera flowers modulates the immune response in vitro of Trypanos

A trypsin inhibitor from Moringa oleifera flowers modulates the immune response in vitro of Trypanosoma cruzi-infected human cells.

causes the lethal Chagas disease , which is endemic in Latin America .
Flowers of ( Moringaceae ) express a trypsin inhibitor ( MoFTI ) whose toxicity totrypomastigotes was previously reported .
Here , we studied the effects of MoFTI on the viability of human peripheral blood mononuclear cells ( PBMCs ) as well as on the production of cytokines and nitric oxide ( NO ) by-infected PBMCs .
Incubation with MoFTI ( trypsin inhibitory activity : 62 U/mg ) led to lysis of trypomastigotes ( LCof 43.5µg/mL ) but did not affect the viability of PBMCs when tested at @ @ @ @ @ @ @ selectivity index > 11.48 was determined .
When-infected PBMCs were treated with MoFTI ( 43.5 or 87.0µg/mL ) , the release of the pro-inflammatory cytokine TNF-α and INF-γ , as well as of NO , was stimulated .
The release of the anti-inflammatory cytokine IL-10 also increased .
In conclusion , the toxicity toand the production of IL-10 by infected PBMCs treated with MoFTI suggest that this molecule may be able to control parasitemia while regulating the inflammation , preventing the progress of Chagas disease .
The data reported here stimulate future investigations @ @ @ @ @ @ @ on immune response in Chagas disease .

causes the lethal Chagas disease, which is endemic in Latin America. Flowers of(Moringaceae) express a trypsin inhibitor (MoFTI) whose toxicity totrypomastigotes was previously reported. Here, we studied the effects of MoFTI on the viability of human peripheral blood mononuclear cells (PBMCs) as well as on the production of cytokines and nitric oxide (NO) by-infected PBMCs. Incubation with MoFTI (trypsin inhibitory activity: 62 U/mg) led to lysis of trypomastigotes (LCof 43.5µg/mL) but did not affect the viability of PBMCs when tested at concentrations up to 500 µg/mL. A selectivity index>11.48 was determined. When-infected PBMCs were treated with MoFTI (43.5 or 87.0µg/mL), the release of the pro-inflammatory cytokine TNF-α and INF-γ, as well as of NO, was stimulated. The release of the anti-inflammatory cytokine IL-10 also increased. In conclusion, the toxicity toand the production of IL-10 by infected PBMCs treated with MoFTI suggest that this molecule may be able to control parasitemia while regulating the inflammation, preventing the progress of Chagas disease. The data reported here stimulate future investigations concerning the in vivo effects of MoFTI on immune response in Chagas disease.


greenmedinfo--2020-09-03--Oral NAC supplementation reduced serum level of CRP and IL-6.

PURPOSE : Randomized Clinical Trials ( RCTs ) have provided varied and conflicting findings regarding the effect of N-acetylcysteine ( NAC ) on inflammatory biomarkers .
This study was conducted to review existing literature to determine whether NAC supplementation can affect inflammatory biomarkers in adults .
METHODS : Bibliographic databases of Scopus , and PubMed were used for relevant papers published until October 2019 .
Results were reported as weighted mean differences ( WMD ) with 95 % confidence intervals ( CI ) using multi-level models .
Cochrane 's Q and I-squared ( I ) tests were used to determine @ @ @ @ @ @ @ RCTs which include 1057 sample size were entered to analysis .
NAC doses and intervention duration ranged from 400 to 2000 mg/d , and 1 to 80 weeks , respectively .
Oral supplementation of NAC reduced serum level of C-reactive protein ( CRP ) [ WMD : -0.61 mg/L , 95 % CI : -1.18 to -0.03 , P = 0.039 , I = 79.6 % ] , and interleukin-6 ( IL-6 ) [ WMD : -0.43 pg/mL , 95 % CI : -0.69 to -0.17 , P = 0.001 , I = @ @ @ @ @ @ @ effect of oral NAC supplementation on other inflammatory biomarkers was nonsignificant .
Dose-response investigation showed a non-linear association between oral NAC supplementation with CRP .
CONCLUSION : Oral NAC supplementation reduced serum level of CRP and IL-6 , but did not affect other inflammatory biomarkers .
Nevertheless , more RCTs seems to be required to explore how NAC in different dosage and different routes of administration can affect inflammatory biomarkers .

PURPOSE: Randomized Clinical Trials (RCTs) have provided varied and conflicting findings regarding the effect of N-acetylcysteine (NAC) on inflammatory biomarkers. This study was conducted to review existing literature to determine whether NAC supplementation can affect inflammatory biomarkers in adults.
METHODS: Bibliographic databases of Scopus, and PubMed were used for relevant papers published until October 2019. Results were reported as weighted mean differences (WMD) with 95% confidence intervals (CI) using multi-level models. Cochrane's Q and I-squared (I) tests were used to determine heterogeneity among studies.
RESULTS: Twenty-four RCTs which include 1057 sample size were entered to analysis. NAC doses and intervention duration ranged from 400 to 2000 mg/d, and 1 to 80 weeks, respectively. Oral supplementation of NAC reduced serum level of C-reactive protein (CRP) [WMD: -0.61 mg/L, 95% CI: -1.18 to -0.03, P = 0.039, I = 79.6%], and interleukin-6 (IL-6) [WMD: -0.43 pg/mL, 95% CI: -0.69 to -0.17, P = 0.001, I = 89.3%]. However, the effect of oral NAC supplementation on other inflammatory biomarkers was nonsignificant. Dose-response investigation showed a non-linear association between oral NAC supplementation with CRP.
CONCLUSION: Oral NAC supplementation reduced serum level of CRP and IL-6, but did not affect other inflammatory biomarkers. Nevertheless, more RCTs seems to be required to explore how NAC in different dosage and different routes of administration can affect inflammatory biomarkers.


greenmedinfo--2020-09-03--N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who

N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy.

BACKGROUNDS AND PURPOSE : Radiation therapy is an important mode of treatment for patients with head and neck cancers , but some associated complications can reduce the quality of life .
We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients .
MATERIALS AND METHODS : We designed a prospective , non-randomized controlled multi-center study involving 10 institutions .
We enrolled 120 patients ( 80 in the experimental group and 40 in the control group ) .
Patients in the experimental group inhaled nebulized liquid N-acetylcysteine ( 2400 mg daily ) for 8 weeks from the @ @ @ @ @ @ @ life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H & N 35 .
RESULTS : N-acetylcysteine inhalation was not associated with any side effect or discomfort .
The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group ( P = 0.014 ) .
Dry mouth symptoms also improved significantly in the experimental group ( P = 0.019 ) .
CONCLUSION : N-acetylcysteine inhalation improves the quality of @ @ @ @ @ @ @ cancers who are receiving radiation therapy , without any specific side effect .

BACKGROUNDS AND PURPOSE: Radiation therapy is an important mode of treatment for patients with head and neck cancers, but some associated complications can reduce the quality of life. We investigated whether N-acetylcysteine inhalation therapy improved the quality of life of such patients.
MATERIALS AND METHODS: We designed a prospective, non-randomized controlled multi-center study involving 10 institutions. We enrolled 120 patients (80 in the experimental group and 40 in the control group). Patients in the experimental group inhaled nebulized liquid N-acetylcysteine (2400 mg daily) for 8 weeks from the start of radiation therapy. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire H&N 35.
RESULTS: N-acetylcysteine inhalation was not associated with any side effect or discomfort. The reduction in painkiller use from the end of N-acetylcysteine inhalation therapy to the 1-month follow-up was greater in the experimental group than in the control group (P = 0.014). Dry mouth symptoms also improved significantly in the experimental group (P = 0.019).
CONCLUSION: N-acetylcysteine inhalation improves the quality of life of patients with head and neck cancers who are receiving radiation therapy, without any specific side effect.


greenmedinfo--2020-09-03--Vitamin D and other anti-inflammatory host-directed therapies medications used as adjunct TB treatme

Vitamin D and other anti-inflammatory host-directed therapies medications used as adjunct TB treatment may be well tolerated and effective.

BACKGROUND : The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis ( TB ) treatment has recently received increasing interest .
There is , therefore , a need to broadly examine current host-directed therapies ( HDTs ) that could accelerate treatment response and improve TB outcomes .
METHODS : This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB .
Sputum smear conversion rate at 4-8 weeks was the primary outcome .
Secondary outcomes included blood indices associated with infectivity and inflammation , chest radiology @ @ @ @ @ @ @ : Fifty-five studies were screened for eligibility after the initial search , which yielded more than 1000 records .
Of the 2540 participants in the 15 trials included in the meta-analysis , 1898 ( 74.7 % ) were male , and the age at entry ranged from 18 to 70 years .
There was a 38 % significantly ( RR 1.38 , 95 % CI = 1.03-1.84 ) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment .
Patients @ @ @ @ @ @ @ addition toTB treatment also had a 29 % significantly increased sputum smear conversion rate ( RR 1.29 , 95 % CI = 1.09-1.563 ) .
Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls ( 3.52 vs 2.70 , 95 % CI for difference 0.16-1.11 , p = 0.009 ) and ( adjusted mean difference 0.4 , 95 % CI 0.2 -- 0.6 ; p = 0.001 ) ; whilst tumour necrosis factor-alpha ( TNF-α ) showed a trend towards a reduction in prednisolone ( @ @ @ @ @ @ @ anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective .
They significantly improved sputum smear conversion rate and chest radiological appearance , and also exhibited an inflammation resolution effect .

BACKGROUND: The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes.
METHODS: This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events.
RESULTS: Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition toTB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments.
CONCLUSIONS: Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.


greenmedinfo--2020-09-03--Crocetin beta-d-glucosyl ester from Crocus sativus biowastes showed antiproliferative effects.

Saffron plant ( L. ) is being used as a source of saffron spice and medicine to cure or prevent @ @ @ @ @ cancers .
We report the isolation , characterization of bioactive small molecule ( [ crocetin @ @ @ @ @ from the leaf biowastes of saffron plant of Kashmir , India .
MTTC assay and @ @ @ @ @ to assess anti-oxidant activity and anti-cancer properties of crocin ( s ) against DPPH free @ @ @ @ @ line respectively .
Crocetin beta-d-glucosyl ester restrained proliferation of human breast adeno-carcinoma cell model ( @ @ @ @ @ normal cell line ( L-6 ) .
Further studies involving molecular mechanics generalized born surface @ @ @ @ @ that crocetin beta-d-glucosyl ester exhibits strong affinity for estrogen receptor alpha and histone deacetylase 2 @ @ @ @ @ breast cancer signalling ) as evidenced by the negative docking score and binding free energy @ @ @ @ @ Therefore , crocetin beta-d-glucosyl ester frombiowastes showed antiproliferative effect possibly by inhibiting estrogen receptor alpha @ @ @ @ @ .

Saffron plant (L.) is being used as a source of saffron spice and medicine to cure or prevent different types of diseases including cancers. We report the isolation, characterization of bioactive small molecule ([crocetin (β-d-glucosyl) ester] from the leaf biowastes of saffron plant of Kashmir, India. MTTC assay and Bio-autography aided approach were used to assess anti-oxidant activity and anti-cancer properties of crocin (s) against DPPH free radical and breast cancer cell line respectively. Crocetin beta-d-glucosyl ester restrained proliferation of human breast adeno-carcinoma cell model (MCF-7) without significantly affecting normal cell line (L-6). Further studies involving molecular mechanics generalized born surface area and molecular docking showed that crocetin beta-d-glucosyl ester exhibits strong affinity for estrogen receptor alpha and histone deacetylase 2 (crucial receptors involved in breast cancer signalling) as evidenced by the negative docking score and binding free energy (BFE) values. Therefore, crocetin beta-d-glucosyl ester frombiowastes showed antiproliferative effect possibly by inhibiting estrogen receptor alpha and HDAC2 mediated signalling cascade.


greenmedinfo--2020-09-03--Safranal ameliorates myocardial ischemia.

Safranal ( SFR ) is the major constituent of saffron .
The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline ( ISO ) and to explore its possible mechanism .
The myocardial ischemia rat model was established by subcutaneous injection of ISO ( 85 mg/kg/d ) on the 8th and 9th day of the experiment .
Serum creatine kinase ( CK ) , lactate dehydrogenase ( LDH ) , malondialdehyde ( MDA ) and superoxide dismutase ( SOD ) were measured , as were changes in calcium concentration , reactive oxygen @ @ @ @ @ @ @ of the myocardial tissue .
The effects of SFR on cell contraction , Catransient and L-type Cacurrent ( I ) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique .
SFR can decrease the activity of serum CK , LDH and MDA , and increase the activity of serum SOD , reduce intracellular calcium concentration and the manufacture of ROS .
In addition , SFR can improve changes in heart morphology .
SFR can significantly inhibit contraction , Catransients and Iin isolated ventricular myocytes @ @ @ @ @ @ @ ISO-induced MI rats , and the underling mechanism is related to the inhibition of oxidative stress , myocardial contractility , Iand the regulation of Cahomeostasis .

Safranal (SFR) is the major constituent of saffron. The purpose of this study was to observe the effect of SFR on myocardial ischemia induced by isoprenaline (ISO) and to explore its possible mechanism. The myocardial ischemia rat model was established by subcutaneous injection of ISO (85 mg/kg/d) on the 8th and 9th day of the experiment. Serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide dismutase (SOD) were measured, as were changes in calcium concentration, reactive oxygen species (ROS) and cardiac morphology of the myocardial tissue. The effects of SFR on cell contraction, Catransient and L-type Cacurrent (I) in isolated rat myocardial cells were measured using the Ion Optix detection system and the whole-cell patch-clamp technique. SFR can decrease the activity of serum CK, LDH and MDA, and increase the activity of serum SOD, reduce intracellular calcium concentration and the manufacture of ROS. In addition, SFR can improve changes in heart morphology. SFR can significantly inhibit contraction, Catransients and Iin isolated ventricular myocytes. SFR has a cardioprotective role in ISO-induced MI rats, and the underling mechanism is related to the inhibition of oxidative stress, myocardial contractility, Iand the regulation of Cahomeostasis.


greenmedinfo--2020-09-03--This data supports a beneficial role for oral saffron in anxious and depressive states.

Anxiety and depression have high prevalence in the general population , affecting millions of people worldwide , but there is still a need for effective and safe treatments .
Nutritional supplements have recently received a lot of attention , particularly saffron .
Thus , several pre-clinical studies support a beneficial role for bioactive compounds , such as saffron , in anxiety and depression .
Here we used an animal model of depression based on social isolation to assess the effects of affron , a standardized saffron extract containing≥3.5 % of total bioactive compounds safranal and crocin isomers .
Affronwas administered @ @ @ @ @ @ @ routes , and several tasks related to anxiety and depression , such as the elevated plus maze , the forced swimming test or the sucrose preference test , were assessed .
These tasks model key features of depressive states and anxious states relating to fear , behavioral despair or anhedonia , the lack of motivation and/or pleasure from everyday activities , respectively .
Animals receiving oral affrondisplayed behaviors congruent with improvements in their anxious/depressive state , showing the enhanced consumption of a sweet solution , as well as an increase in certain escape @ @ @ @ @ @ @ Our data support a beneficial role for oral saffron in anxious/depressive states .

Anxiety and depression have high prevalence in the general population, affecting millions of people worldwide, but there is still a need for effective and safe treatments. Nutritional supplements have recently received a lot of attention, particularly saffron. Thus, several pre-clinical studies support a beneficial role for bioactive compounds, such as saffron, in anxiety and depression. Here we used an animal model of depression based on social isolation to assess the effects of affron, a standardized saffron extract containing≥3.5% of total bioactive compounds safranal and crocin isomers. Affronwas administered both through the oral and the intraperitoneal routes, and several tasks related to anxiety and depression, such as the elevated plus maze, the forced swimming test or the sucrose preference test, were assessed. These tasks model key features of depressive states and anxious states relating to fear, behavioral despair or anhedonia, the lack of motivation and/or pleasure from everyday activities, respectively. Animals receiving oral affrondisplayed behaviors congruent with improvements in their anxious/depressive state, showing the enhanced consumption of a sweet solution, as well as an increase in certain escape responses in the forced swimming test. Our data support a beneficial role for oral saffron in anxious/depressive states.


greenmedinfo--2020-09-03--A traditionally used herbal combination could potentially use as a treatment of cognitive impairment

A traditionally used herbal combination could potentially use as a treatment of cognitive impairment induced by thyroid hormone deficiency.

In the present study , the impact of a combination of four memory-enhancer herbs on cognitive impairment and brain tissue oxidative damage due to hypothyroidism was evaluated .
Propylthiouracil ( PTU ; 0.05 % ) was administrated in drinking water .
Rats were treated with a combination of four herbal products ( Cyperus rotundus , Crocus sativus , Piper nigrum , and Boswellia serrata ) mixed with honey at two doses ( 640 and 1,280 mg/kg ) or donepezil ( 0.5 mg/kg ) , for 6 weeks .
Memory performance on the Morris water maze ( MWM ) and avoidance @ @ @ @ @ @ @ hypothyroidism , and brain tissue oxidative damage occurred .
Herbal combination and donepezil significantly improved memory impairment , reduced malondialdehyde concentration , and nitric oxide metabolites while increased the thiol contents and catalase and superoxide dismutase enzymes activity in the brain .
Our findings suggest that the mixture of herbal products improves learning and memory deficits caused by hypothyroidism , probably byreducing the brain tissue oxidative damage .
PRACTICAL APPLICATIONS : Learning and memory impairment is a common feature of thyroid hormones deficiency .
Several studies are showing that hypothyroidism in juvenile and @ @ @ @ @ @ @ Likewise , in humans , a close relationship between thyroid hormone deficiency and cognitive impairment has been reported .
We used a mixture of herbal products , including Cyperus rotundus , Crocus sativus , Piper nigrum , and Boswellia serrata , to treat hypothyroidism-induced memory impairment .
All these herbs are widely used as a food additive across the world .
In Iranian traditional medicine , this herbal combination traditionally used to treat cognitive impairments .
Numerous studies have indicated that these herbs show neuroprotective and memory-enhancing properties .
Our finding indicated that @ @ @ @ @ @ @ use as a treatment of cognitive impairment induced by thyroid hormone deficiency .

In the present study, the impact of a combination of four memory-enhancer herbs on cognitive impairment and brain tissue oxidative damage due to hypothyroidism was evaluated. Propylthiouracil (PTU; 0.05%) was administrated in drinking water. Rats were treated with a combination of four herbal products (Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata) mixed with honey at two doses (640 and 1,280 mg/kg) or donepezil (0.5 mg/kg), for 6 weeks. Memory performance on the Morris water maze (MWM) and avoidance behavior in passive avoidance was impaired by hypothyroidism, and brain tissue oxidative damage occurred. Herbal combination and donepezil significantly improved memory impairment, reduced malondialdehyde concentration, and nitric oxide metabolites while increased the thiol contents and catalase and superoxide dismutase enzymes activity in the brain. Our findings suggest that the mixture of herbal products improves learning and memory deficits caused by hypothyroidism, probably byreducing the brain tissue oxidative damage. PRACTICAL APPLICATIONS: Learning and memory impairment is a common feature of thyroid hormones deficiency. Several studies are showing that hypothyroidism in juvenile and mature rats induces significant cognitive impairment. Likewise, in humans, a close relationship between thyroid hormone deficiency and cognitive impairment has been reported. We used a mixture of herbal products, including Cyperus rotundus, Crocus sativus, Piper nigrum, and Boswellia serrata, to treat hypothyroidism-induced memory impairment. All these herbs are widely used as a food additive across the world. In Iranian traditional medicine, this herbal combination traditionally used to treat cognitive impairments. Numerous studies have indicated that these herbs show neuroprotective and memory-enhancing properties. Our finding indicated that a traditionally used herbal combination could potentially use as a treatment of cognitive impairment induced by thyroid hormone deficiency.


greenmedinfo--2020-09-03--Phytochemical screening, cytotoxicity and anti-inflammatory activities of the leaf extracts from Law

Phytochemical screening, cytotoxicity and anti-inflammatory activities of the leaf extracts from Lawsonia inermis.

BACKGROUND : Lawsonia inermis Linn popularly known as the Henna has played an important role in ayurvedic or natural herbal medicines .
The presence of phyto-constituents in henna , that may affect the animal or human health adversely , need to be elucidated for L. inermis Linn species grown in India .
INTRODUCTION : The aim of this research was to perform phytochemical , cytotoxicity and anti-inflammatory studies to understand the potential of leaves of Lawsonia inermis of Indian origin to provide a way forward for therapeutic use in medicine .
METHODS : We assessed the phytochemical profile for presence @ @ @ @ @ @ @ glycosides , steroids , flavonoids , saponins , tannins , proteins/amino acids and gums/mucilage ) from various extracts of the plant leaves ' .
The extracts were further purified by column chromatography for the isolation of plant constituents and monitored by TLC , analyzed by Fourier transform infrared FT-IR spectroscopy , H1NMR , and GC-MS analysis .
Fractions were assessed for cytotoxicity and anti-inflammatory properties at various concentrations .
We assessed the anti-inflammatory activity by nitric oxide production in various leaf extracts determined by Griess assay .
RESULTS : All the spectral results @ @ @ @ @ @ @ contain aromatic nucleus and OH group along with methoxy group , allyl as well as vinyl group .
Fractions of chloroform/methanolic ( 7:3 ) leaf extract of Lawsonia inermis confirmed the presence of the two constituents i.e .
fraxetin and 1 ( 3H ) -isobenzofuranone .
We observed significant difference in cytotoxicity at higher concentrations in methanol and chloroform : methanol ( 8:2 ) leaf extracts ( p > 0.05 ) , we could not find any significant differences amongst other leaf extracts at different concentrations .
Some leaf extracts have potential cytotoxic @ @ @ @ @ @ @ chloroform concentration during extraction decreases the cytotoxic effect on the cells .
The nitric oxide levels decreased from 1000µg/ml concentration to lower concentrations with varying degree .
Overall the highest nitric oxide production by CHCl3 ( 70 % ) / MeOH ( 30 % ) was observed amongst various fractions at different concentrations .
CONCLUSION : The phytochemical , cytotoxicity and anti-inflammatory studies indicating the potential of leaves of the plant to provide a way further for their use in medicine .
Fraxetin 1 ( 3H ) -isobenzofuranone structures were confirmed in fractions @ @ @ @ @ @ @ MeOH ( 30 % ) extract as observed as a potent constituents .
Some leaf extracts have potential cytotoxic activity on vero cells .
Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells.The cytotoxicity studies indicates the presence of cytotoxic compounds in some of these extracts , warranting research for fabrication of suitable formulations comprising these constituents to reduce its dose/toxicity for the use of beneficial effects of the plant components .

BACKGROUND: Lawsonia inermis Linn popularly known as the Henna has played an important role in ayurvedic or natural herbal medicines. The presence of phyto-constituents in henna, that may affect the animal or human health adversely, need to be elucidated for L. inermis Linn species grown in India.
INTRODUCTION: The aim of this research was to perform phytochemical, cytotoxicity and anti-inflammatory studies to understand the potential of leaves of Lawsonia inermis of Indian origin to provide a way forward for therapeutic use in medicine.
METHODS: We assessed the phytochemical profile for presence of phyto-constituents (alkaloids, carbohydrates, glycosides, steroids, flavonoids, saponins, tannins, proteins/amino acids and gums/mucilage) from various extracts of the plant leaves'. The extracts were further purified by column chromatography for the isolation of plant constituents and monitored by TLC, analyzed by Fourier transform infrared FT-IR spectroscopy, H1NMR, and GC-MS analysis. Fractions were assessed for cytotoxicity and anti-inflammatory properties at various concentrations. We assessed the anti-inflammatory activity by nitric oxide production in various leaf extracts determined by Griess assay.
RESULTS: All the spectral results suggest that the compounds from the extract contain aromatic nucleus and OH group along with methoxy group, allyl as well as vinyl group. Fractions of chloroform/methanolic (7:3) leaf extract of Lawsonia inermis confirmed the presence of the two constituents i.e. fraxetin and 1(3H)-isobenzofuranone. We observed significant difference in cytotoxicity at higher concentrations in methanol and chloroform:methanol (8:2) leaf extracts (p>0.05), we could not find any significant differences amongst other leaf extracts at different concentrations. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells. The nitric oxide levels decreased from 1000µg/ml concentration to lower concentrations with varying degree. Overall the highest nitric oxide production by CHCl3 (70%)/ MeOH (30%) was observed amongst various fractions at different concentrations.
CONCLUSION: The phytochemical, cytotoxicity and anti-inflammatory studies indicating the potential of leaves of the plant to provide a way further for their use in medicine. Fraxetin 1(3H)-isobenzofuranone structures were confirmed in fractions of CHCl3 (70%)/ MeOH (30%) extract as observed as a potent constituents. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells.The cytotoxicity studies indicates the presence of cytotoxic compounds in some of these extracts, warranting research for fabrication of suitable formulations comprising these constituents to reduce its dose/toxicity for the use of beneficial effects of the plant components.


greenmedinfo--2020-09-03--Topical formulation of henna might be a complementary choice for improving contact dermatitis in pat

BACKGROUND : Contact dermatitis is a common complication in prosthetic limb users .
There are no effective , available and cheap treatments for skin problems of these patients .
In traditional Iranian medicine , henna ( Lawsonia inermis L. ) is a plant that has anti-inflammatory , antimicrobial and skin-enhancing properties , all of which are beneficial for people with artificial limbs .
The aim of this study was to assess the efficacy of a topical henna preparation in management of contact dermatitis in patients using lower limb prosthetics .
METHODS : The current randomized , double-blind , placebo-controlled clinical @ @ @ @ @ @ @ lower extremity amputation using limb prosthetics , aged 12-70 years who complained of contact dermatitis .
They were randomly assigned to receive either two weeks of topical henna preparation every night as the intervention group , or topical placebo as the control group .
Participants were instructed to spread henna preparation on the surfaces of the amputated limb that were in contact with the prosthesis .
Severity of contact dermatitis symptoms was set as the primary outcome measure .
Edema , papules and erythema were evaluated by a physician using standard color atlas @ @ @ @ @ @ @ burning , itching , pain , thickness and skin sweating evaluated by a self-administered questionnaire .
RESULTS : A significant improvement was observed in the symptoms of contact dermatitis including skin edema , itching , sweating , skin thinning and pain ( p-value < 0.05 ) in the henna group compared to the placebo group .
Skin burning decreased more in the henna group compared to the placebo group , but this was not statistically significant ( p-value = 0.052 ) .
Moreover , skin redness significantly increased in the henna group ( @ @ @ @ @ @ @ Topical formulation of henna might be a complementary choice for improving contact dermatitis in patients using lower limb prosthetics .

BACKGROUND: Contact dermatitis is a common complication in prosthetic limb users. There are no effective, available and cheap treatments for skin problems of these patients. In traditional Iranian medicine, henna (Lawsonia inermis L.) is a plant that has anti-inflammatory, antimicrobial and skin-enhancing properties, all of which are beneficial for people with artificial limbs. The aim of this study was to assess the efficacy of a topical henna preparation in management of contact dermatitis in patients using lower limb prosthetics.
METHODS: The current randomized, double-blind, placebo-controlled clinical trial was conducted on ninety-five participants with lower extremity amputation using limb prosthetics, aged 12-70 years who complained of contact dermatitis. They were randomly assigned to receive either two weeks of topical henna preparation every night as the intervention group, or topical placebo as the control group. Participants were instructed to spread henna preparation on the surfaces of the amputated limb that were in contact with the prosthesis. Severity of contact dermatitis symptoms was set as the primary outcome measure. Edema, papules and erythema were evaluated by a physician using standard color atlas. Secondary outcomes included symptoms such as burning, itching, pain, thickness and skin sweating evaluated by a self-administered questionnaire.
RESULTS: A significant improvement was observed in the symptoms of contact dermatitis including skin edema, itching, sweating, skin thinning and pain (p-value<0.05) in the henna group compared to the placebo group. Skin burning decreased more in the henna group compared to the placebo group, but this was not statistically significant (p-value = 0.052). Moreover, skin redness significantly increased in the henna group (p-value = 0.001).
CONCLUSION: Topical formulation of henna might be a complementary choice for improving contact dermatitis in patients using lower limb prosthetics.


greenmedinfo--2020-09-03--In vitro antimalarial and toxicological activities of Quercus infectoria gall extracts.

Background : The spread ofresistance in common antimalarial drugs , including artemisinin-based combination therapies , has necessitated the discovery of new drugs with novel mechanisms of action .
In the present study , the in vitro antimalarial and toxicological activities of acetone , methanol , ethanol and aqueous extracts of ( ) galls were investigated .
Methods : The extracts were assessed for the antimalarial potential using a malarial SYBR Green I fluorescence-based ( MSF ) assay , while the toxicity was screened by using brine shrimp lethality test ( BSLT ) , haemolytic assay , and cytotoxicity assay against @ @ @ @ @ @ @ ) and normal kidney epithelial cell line ( Vero ) .
Results : The acetone extract showed the highest antimalarial activity ( 50 % inhibitory concentration , IC= 5.85± 1.64 μg/mL ) , followed by the methanol extract ( IC= 10.31± 1.90 μg/mL ) .
Meanwhile , the ethanol and aqueous extracts displayed low antimalarial activity with ICvalues of 20.00± 1.57 and 30.95 μg/mL ± 1.27 μg/mL , respectively .
The significant antimalarial activity was demonstrated in all extracts and artemisinin ( < 0.05 ) .
All extracts were non-toxic to brine shrimps @ @ @ @ @ @ @ > 1000 ppm ) .
Furthermore , no occurrence of haemolysis ( < 5 % ) was observed in normal erythrocytes when treated with all extracts compared to Triton X-100 that caused 100 % haemolysis ( < 0.05 ) .
The acetone and methanol extracts were non-toxic to the normal cell lines and statistically significant to artemisinin ( < 0.05 ) .
Conclusion : Taken together with satisfactory selectivity index ( SI ) values , the acetone and methanol extracts ofgalls could serve as an alternative , promising and safe antimalarial agents .

Background: The spread ofresistance in common antimalarial drugs, including artemisinin-based combination therapies, has necessitated the discovery of new drugs with novel mechanisms of action. In the present study, the in vitro antimalarial and toxicological activities of acetone, methanol, ethanol and aqueous extracts of() galls were investigated.
Methods: The extracts were assessed for the antimalarial potential using a malarial SYBR Green I fluorescence-based (MSF) assay, while the toxicity was screened by using brine shrimp lethality test (BSLT), haemolytic assay, and cytotoxicity assay against normal embryo fibroblast cell line (NIH/3T3) and normal kidney epithelial cell line (Vero).
Results: The acetone extract showed the highest antimalarial activity (50% inhibitory concentration, IC= 5.85± 1.64 μg/mL), followed by the methanol extract (IC= 10.31± 1.90 μg/mL). Meanwhile, the ethanol and aqueous extracts displayed low antimalarial activity with ICvalues of 20.00± 1.57 and 30.95 μg/mL ± 1.27 μg/mL, respectively. The significant antimalarial activity was demonstrated in all extracts and artemisinin (<0.05). All extracts were non-toxic to brine shrimps (50% lethality concentration, LC>1000 ppm). Furthermore, no occurrence of haemolysis (<5%) was observed in normal erythrocytes when treated with all extracts compared to Triton X-100 that caused 100% haemolysis (<0.05). The acetone and methanol extracts were non-toxic to the normal cell lines and statistically significant to artemisinin (<0.05).
Conclusion: Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts ofgalls could serve as an alternative, promising and safe antimalarial agents.


greenmedinfo--2020-09-03--The findings showed that the use of henna and oak ointment improves episiotomy wound healing process

The findings showed that the use of henna and oak ointment improves episiotomy wound healing process.

Background : Episiotomy is one of the most common surgical interventions performed to facilitate delivery .
Anti-inflammatory and antibacterial effects of Persian oak ( ) and henna ( ) have been proved in previous studies .
The aim of this study is to evaluate the effect ofandointment on episiotomy wound healing in primiparous women and comparing it with placebo group .
Materials and Methods : This was a double-blind clinical trial conducted on 160 primiparous women who underwent episiotomy .
The cases were randomly selected and divided into four groups of forty patients including control , placebo , those who @ @ @ @ @ @ @ consume topical Persian oak ointment .
Pain and recovery assessment was done at baseline and 7 , 10 , and 14days after birth and measured by Redness , Edema , Ecchymosis , Discharge , and Approximation ( REEDA scale ) and patients ' pain intensity was also measured by a visual analog scale ( VAS ) .
The collected data were analyzed using Chi-square test , one-way ANOVA , and repeated measures ANOVA test by SPSS ( version 22 ) .
Results : The results revealed that according to the reduced score of @ @ @ @ @ @ @ , the wound healing in the henna group and the oak group ( -2.58± 0.29 and - 2.04 ± 0.31 , respectively ) was higher than the control and placebo groups ( -1.62 ± 0.34 and - 1.95 ± 0.32 , respectively ) ( < 0.05 ) .
Furthermore , on the 14day , the mean VAS score was not significantly different between henna and oak groups ( henna group : 2.58± 0.25 and oak group : 2.23 ± 0.18 ) ; however , both intervention groups had a significant difference with the @ @ @ @ @ @ @ ) .
Conclusion : The findings showed that the use of henna and oak ointment improves episiotomy wound healing process , so it is recommended for primiparous women .

Background: Episiotomy is one of the most common surgical interventions performed to facilitate delivery. Anti-inflammatory and antibacterial effects of Persian oak () and henna () have been proved in previous studies. The aim of this study is to evaluate the effect ofandointment on episiotomy wound healing in primiparous women and comparing it with placebo group.
Materials and Methods: This was a double-blind clinical trial conducted on 160 primiparous women who underwent episiotomy. The cases were randomly selected and divided into four groups of forty patients including control, placebo, those who consume topical henna, and those who consume topical Persian oak ointment. Pain and recovery assessment was done at baseline and 7, 10, and 14days after birth and measured by Redness, Edema, Ecchymosis, Discharge, and Approximation (REEDA scale) and patients' pain intensity was also measured by a visual analog scale (VAS). The collected data were analyzed using Chi-square test, one-way ANOVA, and repeated measures ANOVA test by SPSS (version 22).
Results: The results revealed that according to the reduced score of REEDA till the 14day after the delivery, the wound healing in the henna group and the oak group (-2.58± 0.29 and - 2.04 ± 0.31, respectively) was higher than the control and placebo groups (-1.62 ± 0.34 and - 1.95 ± 0.32, respectively) (<0.05). Furthermore, on the 14day, the mean VAS score was not significantly different between henna and oak groups (henna group: 2.58± 0.25 and oak group: 2.23 ± 0.18); however, both intervention groups had a significant difference with the placebo and control groups (<0.05).
Conclusion: The findings showed that the use of henna and oak ointment improves episiotomy wound healing process, so it is recommended for primiparous women.


greenmedinfo--2020-09-03--Ameliorative potential of Lawsonia inermis extract in human lung, colon and liver cancer cell line.

Cancer has emergedas a major public health issue in developed as well as in developing countries .
Plant-derived molecules are widely being used in the treatment of cancer due to their minimum side effects .
( Henna ) is one of the medicinal plants containing many therapeutic properties .
In the present study , bioactive components ofextract were analyzed by LCMS/MS method and validated .
Lawsone ( 3.5 % ) , which is primarily responsible for cytotoxic and anti-cancerous activities .
These properties were studied on human lung carcinoma ( A549 ) , colorectal cancer ( DLD1 ) and Hepatocellular @ @ @ @ @ @ @ .
The activities were assessed by MTT assay , evaluation of apoptosis by measuring the production of Reactive Oxygen Species ( ROS ) and mitochondrial membrane potential of the cancer cell lines .
Moreover , apoptosis in the respective cancer cell lines was also determined by chromatin condensation and DNA fragmentation using Hoechst 33528 and Propidium iodide ( PI ) staining .
The preliminary inresult of MTT showed that the henna extract induces cytotoxic properties against A549 , DLD1 , HepG2 with ICvalues 490µg/ml , 480µg/ml and 610µg/ml respectively ( more than 40 @ @ @ @ @ @ @ , the extract induced a concentration-dependent rise in ROS production which was 84 % , 102 % and 110 % in HepG2 , DLD1 AND A549 respectively at 300µg/ml , whereas at 400µg/ml concentration it was 86 % , 102 % and 106 % in respective cell lines while decreasing mitochondrial membrane potential was more than 20 % in the investigated cell lines .
The extract also provoked changes associated with apoptosis and the data indicate that the ROS production leads to a diminution in mitochondrial membrane potential and thiscorrelated with the extract @ @

Cancer has emergedas a major public health issue in developed as well as in developing countries. Plant-derived molecules are widely being used in the treatment of cancer due to their minimum side effects.(Henna) is one of the medicinal plants containing many therapeutic properties. In the present study, bioactive components ofextract were analyzed by LCMS/MS method and validated. Lawsone (3.5%), which is primarily responsible for cytotoxic and anti-cancerous activities. These properties were studied on human lung carcinoma (A549), colorectal cancer (DLD1) and Hepatocellular carcinoma (HepG2) cancer cell lines. The activities were assessed by MTT assay, evaluation of apoptosis by measuring the production of Reactive Oxygen Species (ROS) and mitochondrial membrane potential of the cancer cell lines. Moreover, apoptosis in the respective cancer cell lines was also determined by chromatin condensation and DNA fragmentation using Hoechst 33528 and Propidium iodide (PI) staining. The preliminary inresult of MTT showed that the henna extract induces cytotoxic properties against A549, DLD1, HepG2 with ICvalues 490µg/ml, 480µg/ml and 610µg/ml respectively (more than 40% growth inhibition). In addition, the extract induced a concentration-dependent rise in ROS production which was 84%, 102% and 110% in HepG2, DLD1 AND A549 respectively at 300µg/ml, whereas at 400µg/ml concentration it was 86%, 102% and 106% in respective cell lines while decreasing mitochondrial membrane potential was more than 20% in the investigated cell lines. The extract also provoked changes associated with apoptosis and the data indicate that the ROS production leads to a diminution in mitochondrial membrane potential and thiscorrelated with the extract cytotoxicity.


greenmedinfo--2020-09-03--Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psor

Shikonin inhibits CEBPD downregulation in IL‑17‑treated HaCaT cells and in an imiquimod‑induced psoriasis model.

Psoriasis is a chronic inflammatory skin disease characterized by well‑defined scaly papules and plaques .
Interleukin ( IL ) ‑17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 ( STAT3 ) activation .
Shikonin , a natural naphthoquinone isolated from Lithospermum erythrorhizon , possesses anti‑inflammatory and immunosuppressive properties and can suppress IL‑17‑induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway .
In the present study , MTS , iCELLigence and RT‑qPCR were used to determine the optimal concentration and duration of IL‑17 or shikonin acting on @ @ @ @ @ @ @ expression levels of genes associated with the IL‑6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array .
Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer‑binding protein δ ( CEBPD ) .
Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod‑induced psoriasis in mice and the expression levels of CEBPD .
Shikonin reversed IL‑17‑mediated downregulation of the tumor suppressor CEBPD in HaCaT cells.Moreover , low levels of CEBPD in the imiquimod‑induced mouse model of psoriasis were restored by shikonin @ @ @ @ @ @ @ .
Taken together , these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy .

Psoriasis is a chronic inflammatory skin disease characterized by well‑defined scaly papules and plaques. Interleukin (IL)‑17 is involved in its pathogenesis and promotes the proliferation of epidermal keratinocytes through signal transducer and activator of transcription 3 (STAT3) activation. Shikonin, a natural naphthoquinone isolated from Lithospermum erythrorhizon, possesses anti‑inflammatory and immunosuppressive properties and can suppress IL‑17‑induced vascular endothelial growth factor expression by inhibiting the JAK/STAT3 pathway. In the present study, MTS, iCELLigence and RT‑qPCR were used to determine the optimal concentration and duration of IL‑17 or shikonin acting on HaCaT cells. The changes in the expression levels of genes associated with the IL‑6/STAT3 pathway in differentially treated cells were analyzed via RT2Profiler™ PCR Array. Small interfering RNA was used to silence the expression levels of the target gene CCAAT/enhancer‑binding protein δ (CEBPD). Western blotting and immunohistochemistry were used to evaluate the effect of shikonin on imiquimod‑induced psoriasis in mice and the expression levels of CEBPD. Shikonin reversed IL‑17‑mediated downregulation of the tumor suppressor CEBPD in HaCaT cells.Moreover, low levels of CEBPD in the imiquimod‑induced mouse model of psoriasis were restored by shikonin treatment, which ameliorated excessive keratinocyte proliferation. Taken together, these findings suggest that CEBPD plays a key role in the pathogenesis of psoriasis and can be targeted by shikonin as a potential therapeutic strategy.


greenmedinfo--2020-09-03--Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvir

Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment.

Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis .
Shikonin , which is extracted from the Chinese herb Zicao ( the dried root of Lithospermum erythrorhizon ) , possesses various pharmacological effects , but its effect on tumor metastasis in the inflammatory microenvironment remains unknown .
In the present study , we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as theunderlying molecular mechanisms .
It was found that , in the inflammatory microenvironment simulated by THP‑1 cell conditioned medium ( THP‑1‑CM ) in vitro @ @ @ @ @ @ @ ( EMT ) , migration and invasion of human lung adenocarcinoma cell lines A549 and H1299 .
In addition , we found that interleukin‑6 ( IL‑6 ) , which is expressed in THP‑1‑CM , promoted the EMT of lung adenocarcinoma cells , and shikonin markedly inhibited IL‑6‑induced EMT and cell motility .
Moreover , shikonin inhibited IL‑6‑induced phosphorylation of signaltransducer and activator of transcription 3 ( STAT3 ) , prevented phosphorylated STAT3 ( p‑STAT3 ) translocation into the nucleus , and suppressed p‑STAT3 transactivation activity .
Additionally , it was found that shikonin @ @ @ @ @ @ @ of p‑STAT3 of A549 cells in vivo .
Furthermore , IL‑6 levels in human lung adenocarcinoma tissues were significantly associated with tumor‑node‑metastasis stage and lymph node metastasis , and its expression was correlated with tumor‑associated macrophage ( TAM ) infiltration .
Together , these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL‑6/STAT3 signaling pathway .

Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis. Shikonin, which is extracted from the Chinese herb Zicao (the dried root of Lithospermum erythrorhizon), possesses various pharmacological effects, but its effect on tumor metastasis in the inflammatory microenvironment remains unknown. In the present study, we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as theunderlying molecular mechanisms. It was found that, in the inflammatory microenvironment simulated by THP‑1 cell conditioned medium (THP‑1‑CM) in vitro, shikonin significantly inhibited the epithelial‑mesenchymal transition (EMT), migration and invasion of human lung adenocarcinoma cell lines A549 and H1299. In addition, we found that interleukin‑6 (IL‑6), which is expressed in THP‑1‑CM, promoted the EMT of lung adenocarcinoma cells, and shikonin markedly inhibited IL‑6‑induced EMT and cell motility. Moreover, shikonin inhibited IL‑6‑induced phosphorylation of signaltransducer and activator of transcription 3 (STAT3), prevented phosphorylated STAT3 (p‑STAT3) translocation into the nucleus, and suppressed p‑STAT3 transactivation activity. Additionally, it was found that shikonin inhibited lung metastasis, EMT and expression of p‑STAT3 of A549 cells in vivo. Furthermore, IL‑6 levels in human lung adenocarcinoma tissues were significantly associated with tumor‑node‑metastasis stage and lymph node metastasis, and its expression was correlated with tumor‑associated macrophage (TAM) infiltration. Together, these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL‑6/STAT3 signaling pathway.


greenmedinfo--2020-09-03--Shikonin is a novel and selective IMPDH2 inhibitor that target triple-negative breast cancer.

Triple-negative breast cancer ( TNBC ) is heterogeneous disease with a poor prognosis .
It is therefore important to explore novel therapeutic agents to improve the clinical efficacy for TNBC .
The inosine 5'-monophosphate dehydrogenase 2 ( IMPDH2 ) is a rate-limiting enzyme in the de novo synthesis of guanine nucleotides .
It is always overexpressed in many types of tumors , including TNBC and regarded as a potential target for cancer therapy .
Through screening a library of natural products , we identified shikonin , a natural bioactive component of Lithospermum erythrorhizon , is a novel and selective IMPDH2 @ @ @ @ @ @ @ indicates that shikonin is a competitive inhibitor of IMPDH2 .
The interaction between shikonin and IMDPH2 was further investigated by thermal shift assay , fluorescence quenching , and molecular docking simulation .
Shikonin treatment effectively inhibits the growth of human TNBC cell line MDA-MB-231 , and murine TNBC cell line , 4T1 in a dose-dependent manner , which is impaired by exogenous supplementation of guanosine , a salvage pathway of purine nucleotides .
Most importantly , IMPDH2 knockdown significantly reduced cell proliferation and conferred resistance to shikonin in TNBC .
Collectively , our @ @ @ @ @ @ @ a selective inhibitor of IMPDH2 with anti-TNBC activity , impelling its further study in clinical trials .

Triple-negative breast cancer (TNBC) is heterogeneous disease with a poor prognosis. It is therefore important to explore novel therapeutic agents to improve the clinical efficacy for TNBC. The inosine 5'-monophosphate dehydrogenase 2 (IMPDH2) is a rate-limiting enzyme in the de novo synthesis of guanine nucleotides. It is always overexpressed in many types of tumors, including TNBC and regarded as a potential target for cancer therapy. Through screening a library of natural products, we identified shikonin, a natural bioactive component of Lithospermum erythrorhizon, is a novel and selective IMPDH2 inhibitor. Enzymatic analysis using Lineweaver-Burk plot indicates that shikonin is a competitive inhibitor of IMPDH2. The interaction between shikonin and IMDPH2 was further investigated by thermal shift assay, fluorescence quenching, and molecular docking simulation. Shikonin treatment effectively inhibits the growth of human TNBC cell line MDA-MB-231, and murine TNBC cell line, 4T1 in a dose-dependent manner, which is impaired by exogenous supplementation of guanosine, a salvage pathway of purine nucleotides. Most importantly, IMPDH2 knockdown significantly reduced cell proliferation and conferred resistance to shikonin in TNBC. Collectively, our findings showed the natural product shikonin as a selective inhibitor of IMPDH2 with anti-TNBC activity, impelling its further study in clinical trials.


greenmedinfo--2020-09-03--Shikonin can be considered a promising treatment for atopic dermatitis.

Atopic dermatitis ( AD ) is a common inflammatory skin disorder .
Shikonin , the active component ofextract , exhibits anti-inflammatory effects .
The objective of the present study was to investigate the effect of shikonin on proinflammatory cytokines and chemokine in patients with AD .
Ten patients with AD who were allergic to house dust mite ( HDM ) and seven healthy controls were recruited in this study .
Peripheral blood mononuclear cells were isolated , and CD14cells were further selected and differentiated to dendritic cells .
Dendritic cells stimulated using Der p 2 , the major HDM allergen @ @ @ @ @ @ @ hours , and dexamethasone was used as a control .
Culture supernatants were collected , and proinflammatory cytokine and chemokine concentrations were analyzed using a multiplex assay system .
Shikonin significantly inhibited Der p 2-induced expression of interleukin ( IL ) -6 , IL-9 , and IL-17A ; monocyte chemoattractant protein ( MCP ) -1 ; macrophage inflammatory protein ( MIP ) -1 ; MIP-1 ; and Chemokine ( C-C motif ) ligand 5 ( RANTES ) .
The inhibitory effects of shikonin on IL-9 , MIP-1 , and RANTES expression were stronger @ @ @ @ @ @ @ Shikonin can be considered a promising drug for AD treatment because it inhibits different inflammatory cytokines expression .

Atopic dermatitis (AD) is a common inflammatory skin disorder. Shikonin, the active component ofextract, exhibits anti-inflammatory effects. The objective of the present study was to investigate the effect of shikonin on proinflammatory cytokines and chemokine in patients with AD. Ten patients with AD who were allergic to house dust mite (HDM) and seven healthy controls were recruited in this study. Peripheral blood mononuclear cells were isolated, and CD14cells were further selected and differentiated to dendritic cells. Dendritic cells stimulated using Der p 2, the major HDM allergen, were cotreated with shikonin for 24 hours, and dexamethasone was used as a control. Culture supernatants were collected, and proinflammatory cytokine and chemokine concentrations were analyzed using a multiplex assay system. Shikonin significantly inhibited Der p 2-induced expression of interleukin (IL)-6, IL-9, and IL-17A; monocyte chemoattractant protein (MCP)-1; macrophage inflammatory protein (MIP)-1; MIP-1; and Chemokine (C-C motif) ligand 5 (RANTES). The inhibitory effects of shikonin on IL-9, MIP-1, and RANTES expression were stronger than those of dexamethasone. Therefore, Shikonin can be considered a promising drug for AD treatment because it inhibits different inflammatory cytokines expression.


greenmedinfo--2020-09-03--Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mecha

Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer.

Colorectal cancer ( CRC ) is a common malignancy occurring in the digestive system .
Despite progress in surgery and therapy options , CRC is still a considerable cause of cancer mortality worldwide .
In this study , a colon cancer patient-derived xenograft model was established to evaluate the antitumor activity of Shikonin .
The protective effect underlying Shikonin was determined through assessing serum levels of liver enzymes ( ALT , AST ) and kidney functions ( BuN , Scr ) in PDX mice .
Proteomics and metabolomics profiles were integrated to provide a systematic perspective in dynamic changes of @ @ @ @ @ @ @ as their perturbed pathways .
A total of 456 differently expressed proteins ( DEPs ) , 32 differently expressed metabolites ( DEMs ) in tumor tissue , and 20 DEMs in mice serum were identified .
The perturbation of arginine biosynthesis , purine metabolism , and biosynthesis of amino acids may mainly account for therapeutic mechanism of Shikonin .
Furthermore , the expression of mRNAs participating in arginine biosynthesis ( CPS1 , OTC , Arg1 ) and do novo purine synthesis ( GART , PAICS , ATIC ) were validated through RT-qPCR .
@ @ @ @ @ @ @ drug therapeutic strategies and a better understanding of antitumor mechanisms that might be valuable for further studies on Shikonin in the clinical treatment of colorectal cancer .

Colorectal cancer (CRC) is a common malignancy occurring in the digestive system. Despite progress in surgery and therapy options, CRC is still a considerable cause of cancer mortality worldwide. In this study, a colon cancer patient-derived xenograft model was established to evaluate the antitumor activity of Shikonin. The protective effect underlying Shikonin was determined through assessing serum levels of liver enzymes (ALT, AST) and kidney functions (BuN, Scr) in PDX mice. Proteomics and metabolomics profiles were integrated to provide a systematic perspective in dynamic changes of proteins and global endogenous metabolites as well as their perturbed pathways. A total of 456 differently expressed proteins (DEPs), 32 differently expressed metabolites (DEMs) in tumor tissue, and 20 DEMs in mice serum were identified. The perturbation of arginine biosynthesis, purine metabolism, and biosynthesis of amino acids may mainly account for therapeutic mechanism of Shikonin. Furthermore, the expression of mRNAs participating in arginine biosynthesis (CPS1, OTC, Arg1) and do novo purine synthesis (GART, PAICS, ATIC) were validated through RT-qPCR. Our study provides new insights into the drug therapeutic strategies and a better understanding of antitumor mechanisms that might be valuable for further studies on Shikonin in the clinical treatment of colorectal cancer.


greenmedinfo--2020-09-03--Melatonin sensitises shikonin-induced cancer cell death.

Recent research suggests that melatonin ( Mel ) , an endogenous hormone and natural supplement , possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies .
Although shikonin ( SHK ) also possesses potential anti-cancer properties , the poor solubility and severe systemic toxicity of this compound hinders its clinical usage .
In this study , we combined Mel and SHK , a potentially promising chemotherapeutic drug combination , with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects .
We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK @ @ @ @ @ @ @ via inhibition of the SIRT3/SOD2-AKT pathway .
Particularly , Mel-SHK treatment induced oxidative stress , increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells , leading to apoptosis .
This drug combination also promoted endoplasmic reticulum ( ER ) stress , leading to AKT dephosphorylation .
In HeLa cells , Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity , while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress , ER stress , mitochondrial dysfunction and apoptosis .
Hence , we propose the combination of Mel and SHK as a @ @ @ @ @ @ @ SIRT3/SOD2-AKT pathway in cancer .

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.