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Pulveroboletus ravenelii (Beck. et Curt.) Murr. (Boletaceae), commonly known as Ravenel's bolete, is an edible and medicinal mushroom, and is also used for preparing mushroom-based dyes. As part of a continuing project to discover the bioactive natural products from wild mushrooms, we analyzed the methanol (MeOH) extract of P. ravenelii to identify metabolites with the anticancer activity. Chemical analysis of the MeOH extract combined with liquid chromatography-mass spectrometry (LC-MS) analysis led to the isolation of a phenolic compound, pulveraven A (PA), whose chemical structure was determined using a combination of 1D and 2D NMR and LC-MS analysis. In the present study, we investigated the cytotoxicity and anticancer mechanisms of pulveraven A using human breast cancer (MCF-7) cells, and demonstrated that it reduced cell viability of MCF-7 cells below 50% (71.74 ± 3.61 μM). Annexin V Alexa Fluor 488 binding assay and western blot results revealed that pulveraven A induced apoptotic cell death via the extrinsic apoptosis pathway, as indicated by the activation of initiator caspase-8 and executioner caspase-7. Furthermore, it was accompanied by an increase in the Bax/Bcl-2 ratio. These results suggest that pulveraven A induces apoptosis in breast cancer cells via the extrinsic apoptotic signaling pathway., (© 2021. The Author(s), under exclusive licence to the Japan Antibiotics Research Association.)

In this study, we examined the neuroprotective effects of MeOH extract and bioactive compounds obtained from Reynoutria elliptica seeds using HT22 cells from the murine hippocampal cell line as its underlying molecular basis, which has not yet been elucidated. Our study showed that the MeOH extract of R. elliptica seeds strongly protected HT22 cells from glutamate toxicity. To clarify the responsible compound for the neuroprotective effects, we took an interest in procyanidins of R. elliptica since procyanidins are known to exhibit high structural diversity and neuroprotective activity. To isolate the procyanidins efficiently, a phytochemical investigation of the MeOH extract from R. elliptica seeds using the LC/MS-guided isolation approach was applied, and procyanidin B2 3″- O -gallate ( 1 ) was successfully isolated. The structure of 1 was elucidated by analyzing the nuclear magnetic resonance spectroscopic data and LC/MS analysis. The neuroprotective activities of 1 were thoroughly examined using HT22 cells. Compound 1 exhibited a strong antioxidant efficacy and blocked glutamate-mediated increase in the reactive oxygen species (ROS) accumulation. Furthermore, compound 1 significantly inhibited the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase, which were increased by glutamate. These findings prove that the extract of R. elliptica seeds containing procyanidin B2 3″-O-gallate, which is a strong neuroprotective component, can be used as a functional food forattenuating and regulating neurological disorders.

A phytochemical investigation of the MeOH extracts from mulberries (the fruit of Morus alba L.) led to the identification of six heterocyclic compounds (1‑6). These compounds were screened to detect whether they protected pancreatic INS‑1 cells from streptozotocin (STZ)‑induced cytotoxicity. Compound 3 was the most effective at preventing STZ‑induced cytotoxicity and the production of reactive oxygen species (ROS) in INS‑1 cells. In addition, compound 3 effectively prevented apoptosis induced by STZ in INS‑1 cells. Compound 3 also prevented STZ‑mediated cleavage of caspase‑8, caspase‑3 and poly (ADP‑ribose) polymerase and increased the expression of B‑cell lymphoma‑2 (Bcl‑2), an anti‑apoptotic Bcl‑2 family protein. In conclusion, the results of the present study indicate that compound 3 extracted from the fruit of M. alba was highly effective in preventing type 1 diabetes mellitus and may be a novel treatment option.

Pinecones from Pinus koraiensisSiebold & Zucc. (Pinaceae), which have historically been treated as an undesired waste by-product in the processing of seeds, have recently been shown to contain ingredients with potent biological activities, such as polyphenols exhibiting antitumor activity. With this study, we seek to broaden our understanding of antitumor compounds contained in these pinecones beyond just polyphenols. We found that the water extract of P. koraiensis pinecones exhibits significant cytotoxic activity, with IC 50 values ranging from 0.62 to 1.73 mg/ml in four human lung cancer cell lines, A549, H1264, H1299, and Calu-6, irrespective of their p53 status. We also demonstrate that pinecone water extract induces apoptosis associated with caspase-3 activation in the same cancer cell lines. Chemical investigation of the pinecone water extract revealed eight main components (1 - 8), and their structures were identified as dehydroabietic acid (1), 15-hydroxy-7-oxodehydroabietic acid (2), 7β,15-dihydroxydehydroabietic acid (3), β-d-glucopyranosyl labda-8(17,13)-diene-(15,16)-lactone-19-oate (4), 7α,15-dihydroxydehydroabietic acid (5), (+)-(1S,2S,4R)-limonene-1,2-diol (6), sobrerol (7), and 4-hydroxybenzoic acid (8). These findings suggest a novel biological application of P. koraiensis pinecones in combatting human lung cancer, and further identify the major compounds that could contribute to this anticancer activity., (© 2017 Wiley-VHCA AG, Zurich, Switzerland.)

This study was performed to investigate the renoprotective effect and mechanism of Momordicae Semen, gac seeds, against the cisplatin-induced damage in LLC-PK1 kidney cells. In order to identify the active components, three major saponins were isolated from extract of the gac seed, gypsogenin 3-O-β-d-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-d-glucuronopyranoside (1), quillaic acid 3-O-β-D-galactopyranosyl(1→2)-[α-L-rhamnopyranosyl(1→3)]-β-D-glucuronopyranoside (2), and momordica saponin I (3). Compounds 1 and 2 ameliorated cisplatin-induced nephrotoxicity up to 80% of the control value at both 5 and 25μM. Phosphorylation of MAPKs was decreased along cisplatin treatment after treatment with compounds 1 and 2. These results show that blocking the MAPKs signaling cascade plays a critical role in mediating the renoprotective effect of Momordicae Semen extract and compounds 1 and 2., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is the fastest-growing tumor capable of spreading to other organs via blood vessels formed by endothelial cells. Apoptosis and angiogenesis-targeting therapies are attractive for cancer treatment. In this study, we aimed to study the in vitro cytotoxicity of Withania somnifera against human HCC (HepG2) cells, identify potential antitumoral withanolide glycosides from the active fraction, and elucidate cytotoxic molecular mechanisms of identified bioactive compounds. W. somnifera (Solanaceae), well-known as 'ashwagandha', is an Ayurvedic medicinal plant used to promote health and longevity, and the MeOH extract of W. somnifera root exhibited cytotoxicity against HepG2 cells during initial screening. Bioactivity-guided fractionation of the MeOH extract and subsequent phytochemical investigation of the active n-BuOH-soluble fraction resulted in the isolation of five withanolide glycosides (1–5), including one new metabolite, withanoside XIII (1), aided by liquid chromatography–mass spectrometry-based analysis. The new compound structure was determined by 1D and 2D nuclear magnetic resonance spectroscopy, high-resolution electrospray ionization mass spectroscopy, electronic circular dichroism, and enzymatic hydrolysis. In addition, withanoside XIIIa (1a) was identified as the new aglycone (1a) of 1. Isolated withanolide glycosides 1–5 and 1a were cytotoxic toward HepG2 cells; withagenin A diglucoside (WAD) (3) exhibited the most potent cytotoxicity against HepG2 cells, with cell viability less than 50% at 100 μM. WAD cytotoxicity was mediated by both extrinsic and intrinsic apoptosis pathways. Treatment with WAD increased protein expression levels of cleaved caspase-8, cleaved caspase-9, cleaved caspase-3, Bcl-2-associated X protein (Bax), and cleaved poly(ADP-ribose) polymerase (cleaved PARP) but decreased expression levels of B-cell lymphoma 2 (Bcl-2). Moreover, WAD inhibited tubular structure formation in human umbilical vein endothelial cells (HUVECs) by inhibiting the protein expression of vascular endothelial growth factor receptor 2 and its downstream pathways, including extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR). These effects were also enhanced by co-treatment with ERK and PI3K inhibitors. Overall, these results indicate that WAD (3) induced HepG2 apoptosis and inhibited HUVEC tube formation, suggesting its potential application in treating liver cancers. [ABSTRACT FROM AUTHOR]

Sorbus commixta Hedl. (Rosaceae) is a well-known herbal tree. Its fruit, commonly called the rowanberry, is traditionally eaten for refreshment and has been used as a laxative and as a gargle for sore throats. We explored the novel pharmacological activity of the S. commixta fruit and found that its ethanolic extracts reduced the viability of human lung adenocarcinoma cells by inducing apoptotic cell death in a p53 -independent manner. Column chromatographic separation of the ethanolic extract led to isolation of three main constituents, benzyl β- d -glucopyranoside, sambunigrin, and prunasin. This is the first report showing the presence of the cyanogenic glycosides, sambunigrin and prunasin, in S. commixta fruit. These findings provide experimental evidence for a novel biological activity of S. commixta fruit against human lung cancer cells and identification of the main constituents, which raise the potential of using S. commixta fruit as a functional food for tumor prevention and management. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • MeOH extract of Pueraria lobata root had significant estrogen-like activities. • Phytochemical analysis of the n -BuOH fraction led to the isolation of 10 isoflavones (1–10). • Genistein (10) had significant estrogen-like activities. • Genistein (10) also exhibited significant cytotoxicity against breast cancer cells. • The cytotoxicity was characterized by the induction of apoptotic cells. Abstract Pueraria lobata root (PLR), well known as Kudzu root, has recently become commercially available in Western dietary supplements for menopausal symptoms. The scientific basis for its action has been attributed to the action of phytoestrogens. This study aimed to investigate the estrogen-like activity of isoflavonoids isolated from P. lobata root and their safety with respect to their effect on breast cancer cell proliferation. In an E-screen assay, crude MeOH extract of PLR significantly increased the proliferation of MCF-7 cells in a concentration-dependent manner. Among the four fractions obtained by solvent fractionation of MeOH extract, the n -BuOH fraction had significant estrogen-like activities at all concentrations tested. Phytochemical analysis of the n -BuOH fraction led to the isolation of 10 isoflavones (1 – 10), among which genistein (10) had significant estrogen-like activities at all concentrations tested. These activities were significantly enhanced by treatment with genistein and 17β-estradiol compared with 17β-estradiol alone, and this effect was mediated by decreased expression of estrogen receptor (ER)α and phospho-ERα in MCF-7 cells. In a cell cytotoxicity assay, genistein (10) exhibited significant cytotoxicity in both ER-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. This cytotoxicity was characterized by the induction of apoptotic cells stained with annexin V conjugated with Alexa Fluor 488 and involved activation of mitochondria-independent and -dependent apoptosis pathways in MCF-7 cells. Our results demonstrated that genistein (10) has estrogen-like effects dependent on ER pathway activation and anti-proliferative effects mediated by the apoptosis pathway rather than the ER pathway in MCF-7 breast cancer cells. [ABSTRACT FROM AUTHOR]