PMID: 

Int J Ophthalmol. 2019 ;12(10):1531-1538. Epub 2019 Oct 18. PMID: 31637187

Abstract Title: 

Parthenolide inhibits the proliferation and induces the apoptosis of human uveal melanoma cells.

Abstract: 

AIM: To explore the effect of parthenolide (PTL) on human uveal melanoma (UM) cells (C918 and SP6.5 cells) and its molecular mechanism.METHODS: Carboxyfluorescein succinimidyl amino ester (CFSE) assays and cell counting kit-8 (CCK-8) were performed to detect the cell viability. Flow cytometry was used to analyze cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were performed to measure proliferation-related and apoptosis-related factors.RESULTS: Firstly, PTL decreased the viability of C918 and SP6.5 cells in a dose-dependent manner, and the effect of PTL on C918 cells was stronger than on SP6.5; however, it did not affect normal cells. Secondly, PTL increased the proportion of cell number at cell cycle G1 phase in C918 cells, and decreased the proportion of cell number at S phase, but the proportion did not change at G2 phase. In addition, PTL induced the apoptosis of C918 cells, and decreased the expressions of Cyclin D1, B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-XL). Also, PTL increased Cyclin inhibition protein 1 (P21), Bcl-2-associated X protein (Bax), Cysteinyl aspartate specific proteinas-3 (Caspase-3) and Caspase-9 expression. However, the expression of Caspase-8 was not changed.CONCLUSION: PTL inhibites proliferation and induces apoptosis in UM cells by arresting G1 phase and regulating mitochondrial pathway, however, it does not affect normal cells.

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PMID: 

Sci Rep. 2019 Dec 18 ;9(1):19370. Epub 2019 Dec 18. PMID: 31852965

Abstract Title: 

Paeonol attenuates inflammation by targeting HMGB1 through upregulating miR-339-5p.

Abstract: 

Sepsis is a life-threatening disease caused by infection. Inflammation is a key pathogenic process in sepsis. Paeonol, an active ingredient in moutan cortex (a Chinese herb), has many pharmacological activities, such as anti-inflammatory and antitumour actions. Previous studies have indicated that paeonol inhibits the expression of HMGB1 and the transcriptional activity of NF-κB. However, its underlying mechanism is still unknown. In this study, microarray assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) results confirmed that paeonol could significantly up-regulate the expression of miR-339-5p in RAW264.7 cells stimulated by LPS. Dual-luciferase assays indicated that miR-339-5p interacted with the 3' untranslated region (3'-UTR) of HMGB1. Western blot, immunofluorescence and enzyme-linked immunosorbent assay (ELISA) analyses indicated that miR-339-5p mimic and siHMGB1 both negatively regulated the expression and secretion of inflammatory cytokines (e.g., HMGB1, IL-1β and TNF-α) in LPS-induced RAW264.7 cells. Studies have confirmed that IKK-β is targeted by miR-339-5p, and we further found that paeonol could inhibit IKK-β expression. Positive mutual feedback between HMGB1 and IKK-β was observed when we silenced HMGB1 or IKK-β. These results indicated that paeonol could attenuate the inflammation mediated by HMGB1 and IKK-β by upregulating miR-339-5p expression. In addition, we constructed CLP model mice by cecal ligation and puncture. Paeonol was used to intervene to investigate its anti-inflammatory effect in vivo. The results showed that paeonol could improve the survival rate of sepsis mice and protect the kidney of sepsis mice.

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Are aching, swollen joints stifling your activity levels and making life a real pain? Read on to learn how ginger, an inexpensive, herbal wonder, can lead to less pain and inflammation

PMID: 

Pharmacol Ther. 2019 Dec 10:107452. Epub 2019 Dec 10. PMID: 31836457

Abstract Title: 

Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony.

Abstract: 

As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhibit inflammation in the animal models of autoimmune diseases, such as experimental arthritis, psoriatic mice and experimental autoimmune encephalomyelitis, and so on. Pae modulates the functions and activation of immune cells, decreases inflammatory medium production, and restores abnormal signal pathway. Pae could balance the subsets of immune cells through inhibiting abnormal activated cell subsets and restoring regulatory cell subsets. Pae could regulate signaling pathways (GPCR pathway, MAPKs /NF-κB patway, PI3K /Akt /mTOR pathway, JAK2 /STAT3 pathway, TGFβ /Smads, and etc.). TGP is composed of Pae, hydroxyl-paeoniflorin, paeonin, albiflorin and benzoylpaeoniflorin etc. Pae accounts for more than 40% of TGP. Like Pae, TGP has anti-inflammatory and immune regulatory effects. TGP has been widely used to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, allergic contact dermatitis, and etc. in China. Furthermore, TGP has some superior features with immune regulation, gentle effect, many indications and few adverse drug reactions. These findings suggest that TGP may be a promising anti-inflammatory and immune drug with soft regulation and has more superiority in the treatment of AIDs. Currently, TGP is used for the treatment of RA, SLE and other AIDs in more than 1000 hospitals in China, which obtained great social and economic benefits.

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PMID: 

Pharmacol Ther. 2019 Dec 10:107452. Epub 2019 Dec 10. PMID: 31836457

Abstract Title: 

Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony.

Abstract: 

As a Traditional Chinese Medicine, Paeonia lactiflora Pallas has been used to treat pain, inflammation and immune disorders for more than 1000 years in China. Total glycoside of paeony (TGP) is extracted from the dried root of Paeonia lactiflora Pallas. Paeoniflorin (Pae) is the major active component of TGP. Our research group has done a lot of work in the pharmacological mechanisms of Pae and found that Pae possessed extensive anti-inflammatory and immune regulatory effects. Pae could inhibit inflammation in the animal models of autoimmune diseases, such as experimental arthritis, psoriatic mice and experimental autoimmune encephalomyelitis, and so on. Pae modulates the functions and activation of immune cells, decreases inflammatory medium production, and restores abnormal signal pathway. Pae could balance the subsets of immune cells through inhibiting abnormal activated cell subsets and restoring regulatory cell subsets. Pae could regulate signaling pathways (GPCR pathway, MAPKs /NF-κB patway, PI3K /Akt /mTOR pathway, JAK2 /STAT3 pathway, TGFβ /Smads, and etc.). TGP is composed of Pae, hydroxyl-paeoniflorin, paeonin, albiflorin and benzoylpaeoniflorin etc. Pae accounts for more than 40% of TGP. Like Pae, TGP has anti-inflammatory and immune regulatory effects. TGP has been widely used to treat autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriasis, allergic contact dermatitis, and etc. in China. Furthermore, TGP has some superior features with immune regulation, gentle effect, many indications and few adverse drug reactions. These findings suggest that TGP may be a promising anti-inflammatory and immune drug with soft regulation and has more superiority in the treatment of AIDs. Currently, TGP is used for the treatment of RA, SLE and other AIDs in more than 1000 hospitals in China, which obtained great social and economic benefits.

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PMID: 

Curr Pharm Biotechnol. 2019 Dec 24. Epub 2019 Dec 24. PMID: 31884927

Abstract Title: 

Protective effect of paeoniflorin on acute cerebral infarction in rats.

Abstract: 

The purpose of this paper was to study the protective effect of paeoniflorin on acute cerebral ischemia. The animal model of cerebral infarction induced by middle cerebral artery occlusion (MCAO) was blocked by suture method. Sixty SD rats were randomly divided into shame group, MCAO group, paeoniflorin (60, 120, 240 mg/kg, respectively) and nimodipine (NMDP) group (n = 10 per group). The rats were intragastrically administered immediately after operation. After 7 days of gavage, the brains were decapitated at 24 h. Hematoxylin and eosin (HE) staining was used to observe the degree of cell damage in the cerebral cortex of rats. Immunohistochemistry was used to detect silver plating and to observe changes in nerve cells. Rats in the model group showed obvious symptoms of neurological deficits, such as the ischemic morphological changed obviously, the malondialdehyde (MDA), lactate dehydrogenase (LD) content and lactate dehydrogenase (LDH) activity was significantly increased in the ischemic brain tissue, while the superoxide dismutase (SOD) activity was decreased. The decrease in Na+-K+-ATPase activity was significantly lower than that in the sham group. The neurological symptoms and signs of MCAO in the different doses of paeoniflorin group were improved, and the neuronal edema in the cortical area was alleviated. The activities of SOD, LDH and Na+-K+-ATPase were significantly increased, and the contents of MDA and LD were decreased. Therefore, paeoniflorin could alleviate the degree of tissue damage in rats with acute cerebral infarction, inhabit the formation of free radicals in the brain tissue after ischemia, and reduce the degree of lipid peroxidation. Thus the degree of cell damage was reduced greatly and a protective effect was showed on cerebral ischemia.

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PMID: 

Int Immunopharmacol. 2019 Dec 12 ;78:106064. Epub 2019 Dec 12. PMID: 31838448

Abstract Title: 

Parthenolide, an NF-κB inhibitor, alleviates peritoneal fibrosis by suppressing the TGF-β/Smad pathway.

Abstract: 

Transforming growth factor (TGF)-β/Smad signalling plays a central role in the pathogenesis of peritoneal fibrosis related to peritoneal dialysis (PD). Parthenolide (PTL), a naturally occurring phytochemical, is isolated from the shoots of feverfew (Tanacetum parthenium) and displays analgesia, anti-inflammation and anticancer activities. In this study, we examined the therapeutic potential of PTL on PD-related peritoneal fibrosis induced by daily intraperitoneal injection of 4.25% dextrose-containing PD fluid (PDF) in vivo and TGF-β1-induced epithelial-mesenchymal transition (EMT) in vitro. PTL was administered daily before PDF injection or after 14 days of PDF injection. Both PTL treatments showed a protective effect on peritoneal fibrosis and prevented peritoneal dysfunction. Similarly, PTL suppressed the expression of fibrotic markers (fibronectin and collagen I) and restored the expression of the epithelial marker (E-cadherin) in TGF-β1-treated HMrSV5 cells. Furthermore, PTL inhibited TGF-β1-induced Smad2 and Smad3 phosphorylation and nuclear translocation but did not influence Smad1/5/9 phosphorylation or activate other downstream signalling pathways of TGF-β1, including AKT, extracellular signal-regulated kinase (ERK) or p38. In conclusion, PTL treatment may represent an effective and novel therapy for PD-associated peritoneal fibrosis by suppressing the TGF-β/Smad pathway.

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PMID: 

Cancers (Basel). 2019 Dec 22 ;12(1). Epub 2019 Dec 22. PMID: 31877856

Abstract Title: 

Honokiol: A Review of Its Anticancer Potential and Mechanisms.

Abstract: 

Cancer is characterised by uncontrolled cell division and abnormal cell growth, which is largely caused by a variety of gene mutations. There are continuous efforts being made to develop effective cancer treatments as resistance to current anticancer drugs has been on the rise. Natural products represent a promising source in the search for anticancer treatments as they possess unique chemical structures and combinations of compounds that may be effective against cancer with a minimal toxicity profile or few side effects compared to standard anticancer therapy. Extensive research on natural products has shown that bioactive natural compounds target multiple cellular processes and pathways involved in cancer progression. In this review, we discuss honokiol, a plant bioactive compound that originates mainly from thespecies. Various studies have proven that honokiol exerts broad-range anticancer activity in vitro and in vivo by regulating numerous signalling pathways. These include induction of G0/G1 and G2/M cell cycle arrest (via the regulation of cyclin-dependent kinase (CDK) and cyclin proteins), epithelial-mesenchymal transition inhibition via the downregulation of mesenchymal markers and upregulation of epithelial markers. Additionally, honokiol possesses the capability to supress cell migration and invasion via the downregulation of several matrix-metalloproteinases (activation of 5' AMP-activated protein kinase (AMPK) and KISS1/KISS1R signalling), inhibiting cell migration, invasion, and metastasis, as well as inducing anti-angiogenesis activity (via the down-regulation of vascular endothelial growth factor (VEGFR) and vascular endothelial growth factor (VEGF)). Combining these studies provides significant insights for the potential of honokiol to be a promising candidate natural compound for chemoprevention and treatment.

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PMID: 

J Microbiol Biotechnol. 2019 Nov 6. Epub 2019 Nov 6. PMID: 31693840

Abstract Title: 

Inhibition of Herpes Simplex Viruses, Types 1 and 2, by Ginsenoside 20(S)-Rg3.

Abstract: 

Infections by herpes simplex viruses have an immense impact on humans, ranging from self-limiting, benign illness to serious, life-threatening diseases. While nucleoside analog drugs are available, resistance has been increasing and currently no vaccine exists. Ginsenosides derived fromhave been documented to inhibit several viruses and bolster immune defenses. This study evaluated 12 of the most relevant ginsenosides fromfor toxicities and inhibition of herpes simplex viruses types 1 and 2 in Vero cells. The effects of test compounds and virus infection were determined using a PrestoBlue cell viability assay. Time course studies were also conducted to better understand at what points the virus life cycle was affected. Non-toxic concentrations of the ginsenosides were determined and ranged from 12.5µM to greater than 100 µM. Ginsenoside 20(S)-Rg3 demonstrated the greatest inhibitory effect and was active against both HSV-1 and HSV-2 with an ICof approximately 35µM. The most dramatic inhibition-over 100% compared to controls-occurred when the virus was exposed to 20(S)-Rg3 for 4 hours prior to being added to cells. 20(S)-Rg3 holds promise as a potential chemotherapeutic agent against herpes simplex viruses and, when used together with valacyclovir, may prevent increased resistance to drugs.

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PMID: 

J Ginseng Res. 2019 Oct ;43(4):550-561. Epub 2018 Apr 9. PMID: 31695563

Abstract Title: 

Evaluation of the gastroprotective effects of 20 (S)-ginsenoside Rg3 on gastric ulcer models in mice.

Abstract: 

Background: Gastric ulcer (GU) is a common gastrointestinal disease that can be induced by many factors. Finding an effective treatment method that contains fewer side effects is important. 20 (S)-ginsenoside Rg3 is a kind of protopanaxadiol and has shown superior antiinflammatory and antioxidant effects in many studies, especially cancer studies. In this study, we examined the treatment efficacy of 20 (S)-ginsenoside Rg3 on GU.
Methods: Three kinds of GU models, including an alcohol GU model, a pylorus-ligated GU model, and an acetic acid GU model, were used. Mouse endothelin-1 (ET-1) and nitric oxide (NO) levels in blood and epidermal growth factor (EGF), superoxide dismutase, and NO levels in gastric mucosa were evaluated. Hematoxylin and eosin staining of gastric mucosa and immunohistochemical staining of ET-1, inducible nitric oxide synthase (NOS2), and epidermal growth factor receptors were studied. Ulcer index (UI) scores and UI ratios were also analyzed to demonstrate the GU conditions in different groups. Furthermore, Glide XP from Schrödinger was used for molecular docking to clarify the interactions between 20 (S)-ginsenoside Rg3 and EGF and NOS2.
Results: 20 (S)-ginsenoside Rg3 significantly decreased the UI scores and UI ratios in all the three GU models, and it demonstrated antiulcer effects by decreasing the ET-1 and NOS2 levels and increasing the NO, superoxide dismutase, EGF, and epidermal growth factor receptor levels. In addition, high-dose 20 (S)-ginsenoside Rg3 showed satisfactory gastric mucosa protection effects.
Conclusion: 20 (S)-ginsenoside Rg3 can inhibit the formation of GU and may be a potential therapeutic agent for GU.