Neopicrorhiza scrophulariiflora (Pennell) Hong: A comprehensive review of its traditional uses, phytochemistry, pharmacology and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Neopicrorhiza scrophulariiflora (Pennell) Hong is important medicinal plant that is native to the eastern Himalayas and Hengduan mountains in China. It is also distributed in Nepal, north east India, Bhutan and northern Myanmar. Plant parts are traditionally used against different kinds of diseases and various compounds present in different plant parts are also effective against many diseases. Thus, N. scrophulariiflora has a high potential to maintain human health. AIM OF THE REVIEW: Although N. scrophulariiflora is very important and widely studied plant species but there is no comprehensive up-to-date review of published and unpublished literature. So, in the present article we have compiled and critically commented on the botanical characteristics, traditional uses, plant growth and cultivation, micropropagation, conservation status, secondary metabolites, pharmacology and toxicity of the plant. MATERIALS AND METHODS: Extensive literature searches both electronic online databases (Google Scholar, Scopus, Springer Link, Web of Science, ScienceDirect, ResearchGate, PubMed, ChemSpider, USPTO, Google patents and Espacenet) and library visits in Nepal were carried out to collect the literature on information published prior to April 2019. RESULTS: N. scrophulariiflora was traditionally used for 82 ailments/diseases. There are 124 major phytochemicals extracted from the plant. Several compounds are effective in bioactivity. Pharmacologically, the plant is proved to be anti-atherosclerotic, antidiabetic and anti-inflammatory in-vivo studies, and antimicrobial, antimalarial, antioxidative, hepatoprotective, immunomodulatory and nerve growth factor potentiating from in-vitro studies. Renal improvement activities were confirmed from both in-vivo and in-vitro studies. Toxicological tests and a single clinical trial in human beings have supported the notion that the plant is not poisonous but beneficial for curing wide ranges of diseases. CONCLUSION: N. scrophulariiflora is valuable medicinal plant that can serve as promising source of non-harmful and potential medicinal herbal remedies for human beings.

Salinomycin induces apoptosis via death receptor-5 up-regulation in cisplatin-resistant ovarian cancer cells.

BACKGROUND: Chemo-resistance to cisplatin-centered cancer therapy is a major obstacle to effective disease treatment. Recently, salinomycin was proven to be highly-effective for the elimination of cancer stem cells both in vitro and in vivo. The objective of the present study was to evaluate the anticancer properties of salinomycin in cisplatin-resistant ovarian cancer cells (A2780cis). MATERIALS AND METHODS: The tetrazolium dye (MTT) assay was used to determine cell viability. Flow cytometric analysis was performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis-related proteins was evaluated by western blot analysis. RESULTS: Cell viability was significantly reduced by salinomycin treatment in a dose-dependent manner. Flow cytometry showed an increase in sub-G1 phase cells. Salinomycin increased the expression of death receptor-5 (DR5), caspase-8 and Fas-associated protein with death domain (FADD). A decline in the expression of FLICE-like inhibitory protein (FLIP), activation of caspase-3 and increased poly ADP-ribose polymerase (PARP) cleavage, triggered apoptosis. Furthermore, annexin-V staining also revealed the apoptotic induction. CONCLUSION: These findings provide important insights regarding the activation of caspase-8 and DR5, to our knowledge, for the first time in salinomycin-treated cisplatin-resistant ovarian cancer and demonstrate that salinomycin could be a prominent anticancer agent.

The synergistic apoptotic interaction of Indole-3-Carbinol and Genistein with TRAIL on endometrial cancer cells.

Induction of apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. The purpose of this study was to determine whether Indole-3-Carbinol (I3C) and Genistein in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis in endometrial cancer cell (Ishikawa) and to assess apoptotic mechanism. The MTT assay and flow cytometry were performed to determine cell viability and cell cycle. The induction of apoptosis was measured by caspase-3 activity test, DNA fragmentation assay, annexin V binding assay and western blot analysis. There was no effect in cell growth inhibition and cell cycle progression alone or in two-combination. However, the treatment of I3C and Genistein followed by TRAIL showed significant cell death and marked increase in sub-G1 arrest. Three-combination treatment revealed elevated expression of DR4, DR5 and cleaved forms of caspase-3, caspase-8, PARP. The Flip was found down regulated. Moreover, increase in caspase-3 activity and DNA fragmentation indicated the induction of apoptosis. The results indicate that I3C and Genistein with TRAIL synergistically induced apoptosis via death receptor dependent pathway. Our findings might provide a new insight into the development of novel combination therapies against endometrial cancer.

Salinomycin inhibits Akt/NF-κB and induces apoptosis in cisplatin resistant ovarian cancer cells.

BACKGROUND: Despite advances in treatment, ovarian cancer is the most lethal gynecologic malignancy. Therefore significant efforts are being made to develop novel strategies for the treatment of ovarian cancer. Salinomycin has been shown to be highly effective in the elimination of cancer stem cells both in vitro and in vivo. The present study focused on investigating important cell signaling molecules such as Akt and NF-κB during salinomycin-induced apoptosis in cisplatin resistant ovarian cancer cells (A2780cis). METHODS: MTT assay was performed to determine cell viability. Flow cytometry and DNA fragmentation assay were performed to analyze the effect on cell cycle and apoptosis. The expression of apoptosis related proteins was evaluated by Western blot analysis. RESULTS: The cell viability was significantly reduced by salinomycin treatment in a dose dependent manner. The flow cytometry result showed an increase in sub-G1 phase. Salinomycin inhibited the nuclear transportation of NF-κB, and downregulated Akt expression. Declined Bcl-2, activation of caspase-3 and increased PARP cleavage triggered apoptosis. Moreover, DNA fragmentation assay also revealed apoptotic induction. CONCLUSION: The result suggested that salinomycin-induced apoptosis in A2780cis was associated with inhibition of Akt/NF-κB. It may become a potential chemotherapeutic agent for the cisplatin resistant ovarian cancer therapy.