Discovery and development of new potentially selective anticancer agents are necessary to prevent a global cancer health crisis. Currently, alternative medicinal agents derived from plants have been extensively investigated to develop anticancer drugs with fewer adverse effects. Among them, steroidal alkaloids are conventional secondary metabolites that comprise an important class of natural products found in plants, marine organisms and invertebrates, and constitute a judicious choice as potential anti‐cancer leads. Traditional medicine and modern science have shown that representatives from this compound group possess potential antimicrobial, analgesic, anticancer and anti‐inflammatory effects. Therefore, systematic and recapitulated information about the bioactivity of these compounds, with special emphasis on the molecular or cellular mechanisms, is of high interest. In this review, we methodically discuss thein vitroandin vivopotential of the anticancer activity of natural steroidal alkaloids and their synthetic and semi‐synthetic derivatives. This review focuses on cumulative and comprehensive molecular mechanisms, which will help researchers understand the molecular pathways involving steroid alkaloids to generate a selective and safe new lead compound with improved therapeutic applications for cancer prevention and therapy.In vitroandin vivostudies provide evidence about the promising therapeutic potential of steroidal alkaloids in various cancer cell lines, but advanced pharmacokinetic and clinical experiments are required to develop more selective and safe drugs for cancer treatment.

Ovarian cancer is a common cause of death among gynecological cancers. Although ovarian cancer initially responds to chemotherapy, frequent recurrence in patients remains a therapeutic challenge. Pyruvate kinase M2 (PKM2) plays a pivotal role in regulating cancer cell survival. However, its therapeutic role remains unclear. Here, we investigated the anticancer effects of compound 3K, a specific PKM2 inhibitor, on the regulation of autophagic and apoptotic pathways in SK-OV-3 (PKM2-overexpressing human ovarian adenocarcinoma cell line). The anticancer effect of compound 3K was examined using MTT and colony formation assays in SK-OV-3 cells. PKM2 expression was positively correlated with the severity of the tumor, and expression of pro-apoptotic proteins increased in SK-OV-3 cells following compound 3K treatment. Compound 3K induced AMPK activation, which was accompanied by mTOR inhibition. Additionally, this compound inhibited glycolysis, resulting in reduced proliferation of SK-OV-3 cells. Compound 3K treatment suppressed tumor progression in an in vivo xenograft model. Our findings suggest that the inhibition of PKM2 by compound 3K affected the Warburg effect and induced autophagic cell death. Therefore, use of specific PKM2 inhibitors to block the glycolytic pathway and target cancer cell metabolism represents a promising therapeutic approach for treating PKM2-overexpressing ovarian cancer.

The purpose of the study is to investigate potential of antioxidant property of ethanolic root extract of Asparagus racemosus Linn (EEAR). In vitro evaluation antioxidant property of EEAR was done using various methods like DPPH scavenging activity, hydroxyl radical scavenging activity, and nitric oxide scavenging activity. HPTLC fingerprint analysis was performed for qualitative determination of possible number of components from the ethanolic extract. Acute toxicity study was performed in Wistar rat and an OECD guideline 423 was followed. The yield value was found 0.96% from EEAR. A concentration of 468.57 ± 3.002 μg/ml of probable antioxidant material from EEAR was required to scavenge 50% of DPPH. The IC50 value of EEAR were found to be 508.17 ± 7.37 μg and 416.57 ± 5.08 μg when determined by hydroxyl radical and nitric oxide scavenging assay respectively. The reducing powers of EEAR was 0.295 ± 0.0037 at 125 μg/ml and increased to 0.934 ± 0.0005 at 500 μg/ml. HPTLC fingerprint data supports several basic informations like isolation, purification, quality evaluation and standardization. No sign of toxicity was observed after treated with 2000 mg/kg of EEAR. The obtained data highlight the potential role of EEAR as a source of natural antioxidants.

Sirtuin (SIRT) is known to prevent nonalcoholic fatty liver disease (NAFLD); however, the role of SIRT4 in the progression of hepatic fibrosis remains unknown. We hypothesize that EX-527, a selective SIRT1 inhibitor, can inhibit the progression of high-fat diet (HFD)-induced hepatic fibrosis. We found that SIRT4 expression in the liver of NAFLD patients is significantly lower than that in normal subjects. In this study, EX-527 (5 µg/kg), administered to HFD rats twice a week for ten weeks, reduced the serum levels of triglyceride (TG), total cholesterol, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and attenuated hepatic fibrosis evidenced by Masson’s trichrome and hepatic fat by oil red-O staining. EX-527 upregulated SIRT2, SIRT3, and SIRT4 expression in the liver of HFD fed rats but downregulated transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression. It decreased proinflammatory cytokine production and hydroxyproline levels in the serum and SMAD4 expression and restored apoptotic protein (Bcl-2, Bax, and cleaved caspase-3) expression. These data propose a critical role for the SIRT4/SMAD4 axis in hepatic fibrogenesis. SIRT4 upregulation has the potential to counter HFD-induced lipid accumulation, inflammation, and fibrogenesis. We demonstrate that EX-527 is a promising candidate in inhibiting the progression of HFD-induced liver fibrosis.