Acanthopanax senticosus ameliorates steatohepatitis through HNF4 alpha pathway activation in mice.

Non-alcoholic fatty liver disease is a common liver disease worldwide, and is associated with dysregulation of lipid metabolism, leading to inflammation and fibrosis. Acanthopanax senticosus Harms (ASH) is widely used in traditional medicine as an adaptogen food. We examined the effect of ASH on steatohepatitis using a high-fat diet mouse model. Mice were fed a choline-deficient, L-amino acid-defined, high-fat diet with ASH extract (ASHE). After 6 weeks, liver RNA transcriptome sequencing (RNA-Seq) was performed, followed by Ingenuity Pathway Analysis (IPA). Our findings revealed that mice fed a high-fat diet with 5% ASHE exhibited significantly reduced liver steatosis. These mice also demonstrated alleviated inflammation and reduced fibrosis in the liver. IPA of RNA-Seq indicated that hepatocyte nuclear factor 4 alpha (HNF4 alpha), a transcription factor, was the activated upstream regulator (P-value 0.00155, z score = 2.413) in the liver of ASHE-fed mice. Adenosine triphosphate binding cassette transporter 8 and carboxylesterase 2, downstream targets of HNF4 alpha pathway, were upregulated. Finally, ASHE-treated HepG2 cells exposed to palmitate exhibited significantly decreased lipid droplet contents. Our study provides that ASHE can activate HNF4 alpha pathway and promote fat secretion from hepatocytes, thereby serving as a prophylactic treatment for steatohepatitis in mice.

Effects of n-3 polyunsaturated fatty acid supplementation on quadriceps weakness immediately after total knee arthroplasty: a pilot, randomized, open-label clinical trial.

[Purpose] Severe quadriceps weakness immediately after total knee arthroplasty can be problematic. The n-3 long-chain polyunsaturated fatty acids have antioxidant and anti-inflammatory effects against ischemia-reperfusion injury, whereas n-6 long-chain polyunsaturated fatty acids exert pro-inflammatory effects, thereby promoting ischemia-reperfusion injury. [Participants and Methods] We explored the efficacy of preoperative n-3 long-chain polyunsaturated fatty acid supplementation against early quadriceps weakness among 20 patients scheduled for total knee arthroplasty (intervention group, n=10; control group, n=10). The intervention group received 645 mg of eicosapentaenoic acid) and 215 mg of docosahexaenoic acid daily for 30 days preoperatively. Serum eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid levels were measured preoperatively. We compared serum derivatives of reactive oxygen metabolites as oxidative stress biomarkers, knee circumference, thigh volume, knee pain during the quadriceps strength test, and quadriceps strength preoperatively and 4 days postoperatively to quantify the change. [Results] Preoperative n-3 long-chain polyunsaturated fatty acid supplementation significantly increased the (eicosapentaenoic acid+docosahexaenoic acid)/arachidonic acid ratio in the intervention group. A significantly lower increase in quadriceps weakness was exhibited in the intervention group than in the control group. However, changes in oxidative stress, knee/thigh swelling, and knee pain during strength testing did not significantly differ between the two groups. [Conclusion] Preoperative n-3 long-chain polyunsaturated fatty acid supplementation exhibited beneficial effects on quadriceps weakness immediately after total knee arthroplasty.

Acanthopanax senticosus Harms extract causes G0/G1 cell cycle arrest and autophagy via inhibition of Rubicon in human liver cancer cells.

Acanthopanax senticosus (Rupr. et Maxim) Harms (ASH), also known as Siberian ginseng or eleuthero, is a hardy shrub native to China, Korea, Russia and the northern region of Japan. ASH is used for the treatment of several diseases such as heart disease, hypertension, rheumatoid arthritis, allergies, chronic bronchitis, diabetes and cancer. In the present study, the inhibitory effect of the root extract of ASH (ASHE) on HuH­7 and HepG2 liver cancer cells was examined. ASHE suppressed liver cancer cell proliferation by inducing cell cycle arrest at the G0/G1 phase, as well as apoptosis, as indicated by the increased number of Annexin V and 7­AAD­positive cells. Furthermore, the expression of LC3­II, an autophagy marker, in these cells also increased post treatment with ASHE. LC3­II induction was further enhanced by co­treatment with chloroquine. Fluorescence and transmission electron micrographs of ASHE­treated liver cancer cells showed the presence of an increased number of autophagic vesicles. A decreased protein expression level of run domain Beclin­1­interacting and cysteine­rich domain­containing, an autophagy inhibitor, with no change in RUBCN mRNA expression was observed, indicating activation of the autophagosome­lysosome fusion step of autophagy. In conclusion, ASHE exerts cytostatic activity on liver cancer cells via both apoptosis and autophagy, and may serve as a potential therapeutic agent for management of liver cancer and autophagy­related diseases.

Prophylactic and therapeutic effects of Acanthopanax senticosus Harms extract on murine collagen-induced arthritis.

Evidences are accumulating that extract of Acanthopanax senticosus Harms (ASH; syn Eleutherococcus senticosus [Rupr. & Maxim.] Maxim), a shrub native to Northeastern Asia, has antiinflammatory effects. In this study, we examined prophylactic and therapeutic effects of ASH extract (ASHE) on rheumatoid arthritis using collagen-induced arthritis (CIA) mouse model. Acanthopanax senticosus Harms extract was administered before the onset of arthritis in the prophylaxis model. In the therapeutic model, ASHE was administered after the onset of arthritis with or without anti-TNF-α antibody. The ASHE treatment showed efficacy before onset of CIA but there was no effect after CIA was established. The ASHE treatment delayed the onset and decreased severity of CIA. In vitro examinations showed that ASHE is an antioxidant and that ASHE suppresses TNF-α and interleukin-6 production in human peripheral blood mononuclear cells. The combination therapy with ASHE and anti-TNF-α antibody reduced the severity of arthritis compared with anti-TNF-α antibody alone. The present study shows that ASHE has prophylactic effect against CIA and support therapeutic effect of anti-TNF-α antibody.