Effects of the Tibetan medicine Byur dMar Nyer lNga Ril Bu on Alzheimer's disease in mice models.

ETHNOPHARMACOLOGICAL RELEVANCE: Byur dMar Nyer lNga Ril Bu (BdNlRB) is a classic Tibetan medicine prescription for treating " white vein disease". Alzheimer's disease (AD) is a chronic degenerative disease of the central nervous system, characterized by distinct "white vein disease". In the absence of effective drugs for AD, BdNlRB may be a possible treatment for AD. AIM OF THE STUDY: To verify the therapeutic effect and possible mechanism of the proved Tibetan medicine BdNlRB on Alzheimer's disease. MATERIALS AND METHODS: 60 APP/PS1 double transgenic AD mice (Mt) and 60 Aß1-40 protein-induced AD mice (Mi) were divided into 3 groups according to the dose of BdNlRB: BdNlRB-100, BdNlRB-200 and BdNlRB-400, with 100, 200 and 400 mg/kg*weight, respectively. The mice were administrated by gavage for 8 weeks. The cognitive ability of mice was detected by Morris Water Maze, the expression of Aß protein, p-tau and microglia was detected by immunofluorescent staining, the protein expression in the hippocampus was detected by proteomics, and the abundance of fecal intestinal flora was detected by 16S RNA. RESULTS: The learning ability and memory ability of Mi mice were significantly improved after BdNlRB administration. The learning ability of Mt mice was significantly improved, while the memory ability was not improved after BdNlRB administration. After the treatment with low and medium doses of BdNlRB, the expression of p-tau decreased significantly (the rate of decrease in BdNlRB-100 and BdNlRB-200 groups was 8.05% and 12.7%, respectively), and the number of microglia increased (39.3% and 31.6%, respectively). BdNlRB significantly affected the protein expression in the hippocampus of Mt mice. 382 proteins in different expression in all three groups mainly involved in amino acid synthesis, fatty acid degradation, glutamine metabolism, synaptic vesicular cycle and oxidative phosphorylation, PPAR signaling pathway and Fc gamma-mediated phagocytosis were activated. Meanwhile, the administration of BdNlRB can regulate the intestinal flora of Mt mice, which reduces the abundance of Muribaculum and uncultured bacteroidales bacterium, and improves the abundance of Ruminococcus-1 and Ruminiclostridium-9. CONCLUSION: The oral administration of BdNlRB significantly improved the cognitive ability of AD mice, and neuroinflammation and intestinal flora regulation were the possible mechanisms.

Protective Effect of Triphala against Oxidative Stress-Induced Neurotoxicity.

BACKGROUND: Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H2O2) and acrylamide. Triphala is a well-recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti-inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. MATERIALS AND METHODS: An in vitro H2O2-induced SH-SY5Y cell model and an in vivo acrylamide-induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H2O2 was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide-induced oxidative injury in Danio rerio was determined using immunofluorescence staining. RESULTS: The results indicated that Triphala plays a neuroprotective role against H2O2 toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen-activated protein kinase (MARK) signal pathway (p-Erk1/2, p-JNK1/2, and p-p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H2O2-treated SH-SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide-induced oxidative stress. CONCLUSION: In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH-SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

An Integrated Study on the Antitumor Effect and Mechanism of Triphala Against Gynecological Cancers Based on Network Pharmacological Prediction and In Vitro Experimental Validation.

OBJECTIVES: Triphala is a herbal medicine that has been widely used for treating a variety of ailments. This study aims to systematically analyze the antitumor effects of Triphala on gynecological cancers. METHODS: The antineoplastic activities of Triphala on gynecological cancers were analyzed using network pharmacology-based strategies. Afterward, the human ovarian cancer cell line SK-OV-3, cervical cancer cell line HeLa, and endometrial cancer cell line HEC-1-B were selected for experimetal valification. RESULTS: Network pharmacology analysis suggested that Triphala could comprehensively intervene in proliferation and apoptosis through diverse signaling pathways, mainly including MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53. The Cell Counting Kit 8 (CCK-8) assay illustrated that Triphala was able to inhibit cell proliferation with half inhibition concentration (IC50) values of 98.28 ± 13.71, 95.56 ± 8.94, and 101.23 ± 7.76 µg/mL against SK-OV-3, HeLa, and HEC-1-B cells, respectively. The ELISA experiment demonstrated that Triphala was capable of promoting programmed cell death, with dosage correlations. The antiproliferative and proapoptotic activities were confirmed by flow cytometric analysis using Ki67 antibody and Annexin V/propidium iodide (PI) dual staining. Western blotting revealed a decrease in expression levels of phospho-Akt, phospho-p44/42, and phospho-NF-κB p56 in cells administered Triphala, which indicated that the possible mechanism could involve downregulation of MAPK/ERK, PI3K/Akt/mTOR, and NF-κB/p53 signaling pathways, as was predicted. CONCLUSION: Triphala holds great promise for treating gynecological cancers. Although the favorable pharmacological properties have been preliminarily investigated in this study, further studies are still needed to uncover the sophisticated mechanism of Triphala in cancer therapy.

Triphala Suppresses Growth and Migration of Human Gastric Carcinoma Cells In Vitro and in a Zebrafish Xenograft Model.

OBJECTIVES: Triphala is an extensively prescribed traditional medicinal formula with potential therapeutic effects on various malignancies such as breast, colon, pancreas, prostate, ovarian, cervical, endometrial, and lymphatic cancer as well as melanoma. This study aimed to investigate Triphala for antitumor activities against gastric cancers. METHODS: In vitro tumor growth and migration of human gastric cancer cells were examined using the CCK-8 and Transwell assays, respectively. In vivo tumor progression was studied in a zebrafish xenograft model. The anticancer activity of Triphala was quantified as growth and metastasis inhibition rate. The underlying molecular mechanism was investigated by Western blotting. RESULTS: The CCK-8 and Transwell experiments indicated that Triphala significantly decreased tumor proliferation and suppressed cell migration in vitro. The zebrafish xenograft study revealed that administration of Triphala inhibited the xenograft growth and metastasis of transplanted carcinoma cells in vivo. Western blotting analysis demonstrated an inhibition of phosphorylation of EGFR, Akt, and ERK in the presence of Triphala, indicating that its antineoplastic mechanism is associated with the regulation of the EGFR/Akt/ERK signaling cascade. CONCLUSION: Triphala is a promising antineoplastic agent for the treatment of gastric carcinomas with significant antiproliferative and antimetastatic activities.

Experimental study of the inhibition effect of "Phrul sByor Chem Mo": a Tibetan medical prescription, on digestive system tumor cell lines in vitro / 中国生化药物杂志

Objective To investigate the inhibition effects of "Phrul sByor Chem Mo (PBCM)" against different common digestive system tumor cell lines in vitro, including human gastric carcinoma cell line MGC803, colorectal carcinoma cell line LoVo, and hepatocellular carcinoma cell line HepG2. Methods The digestive system tumor cell lines in the logarithmic growth phase were incubated with different concentrations of PBCM for 48h. The cell viability was investigated by MTT assays, apoptosis was detected by Hoechst 33342 assays, and the level of Bcl-2 and Bax was estimated by ELISA tests. Results MTT assays proved that the proliferation of digestive system tumor cell lines was significantly inhibited by PBCM in vitro. Fluorescent staining demonstrated that PBCM was able to promote apoptosis of the cell lines. ELISA tests illustrated that the level of proapoptotic Bax was elevated, while the value of antiapoptotic Bcl-2 was decreased. Conclusion PBCM is able to inhibit proliferation and induce apoptosis of digestive system tumor cell lines in vitro. The mechanism may be related with Bcl-2 family proteins.

Experimental study of the inhibition effect of "Phrul sByor Chem Mo": a Tibetan medical prescription, on digestive system tumor cell lines in vitro / 中国生化药物杂志

Objective To investigate the inhibition effects of "Phrul sByor Chem Mo (PBCM)" against different common digestive system tumor cell lines in vitro, including human gastric carcinoma cell line MGC803, colorectal carcinoma cell line LoVo, and hepatocellular carcinoma cell line HepG2. Methods The digestive system tumor cell lines in the logarithmic growth phase were incubated with different concentrations of PBCM for 48h. The cell viability was investigated by MTT assays, apoptosis was detected by Hoechst 33342 assays, and the level of Bcl-2 and Bax was estimated by ELISA tests. Results MTT assays proved that the proliferation of digestive system tumor cell lines was significantly inhibited by PBCM in vitro. Fluorescent staining demonstrated that PBCM was able to promote apoptosis of the cell lines. ELISA tests illustrated that the level of proapoptotic Bax was elevated, while the value of antiapoptotic Bcl-2 was decreased. Conclusion PBCM is able to inhibit proliferation and induce apoptosis of digestive system tumor cell lines in vitro. The mechanism may be related with Bcl-2 family proteins.