Ginkgo biloba L. stands as one of the oldest living tree species, exhibiting a diverse range of biological activities, including antioxidant, neuroprotective, anti-inflammatory, and cardiovascular activities. As part of our ongoing discovery of novel bioactive components from natural sources, we directed our focus toward the investigation of potential bioactive compounds from G. biloba fruit. The profiles of its chemical compounds were examined using a Global Natural Products Social (GNPS)-based molecular networking analysis. Guided by this, we successfully isolated and characterized 11 compounds from G. biloba fruit, including (E)-coniferin (1), syringin (2), 4-hydroxybenzoic acid 4-O-β-D-glucopyranoside (3), vanillic acid 4-O-β-D-glucopyranoside (4), syringic acid 4-O-β-D-glucopyranoside (5), (E)-ferulic acid 4-O-β-D-glucoside (6), (E)-sinapic acid 4-O-β-D-glucopyranoside (7), (1′R,2′S,5′R,8′S,2′Z,4′E)-dihydrophaseic acid 3′-O-β-D-glucopyranoside (8), eucomic acid (9), rutin (10), and laricitrin 3-rutinoside (11). The structural identification was validated through a comprehensive analysis involving nuclear magnetic resonance (NMR) spectroscopic data and LC/MS analyses. All isolated compounds were evaluated using an E-screen assay for their estrogen-like effects in MCF-7 cells. As a result, compounds 2, 3, 4, 8, and 9 promoted cell proliferation in MCF-7 cells, and these effects were mitigated by the ER antagonist, ICI 182,780. In particular, cell proliferation increased most significantly to 140.9 ± 6.5% after treatment with 100 µM of compound 2. The mechanism underlying the estrogen-like effect of syringin (2) was evaluated using a Western blot analysis to determine the expression of estrogen receptor α (ERα). We found that syringin (2) induced an increase in the phosphorylation of ERα. Overall, these experimental results suggest that syringin (2) can potentially aid the control of estrogenic activity during menopause.

Nephrotoxicity is a serious side effect of cisplatin, which is one of the most frequently used drugs for cancer treatment. This study aimed to assess the renoprotective effect of Artemisia absinthium extract and its bioactive compound (shikimic acid) against cisplatin-induced renal injury. An in vitro assay was performed in kidney tubular epithelial cells (LLC-PK1) with 50, 100, and 200 µg/mL A. absinthium extract and 25 and 50 µM shikimic acid, and cytotoxicity was induced by 25 µM cisplatin. BALB/c mice (6 weeks old) were injected with 16 mg/kg cisplatin once and orally administered 25 and 50 mg/kg shikimic acid daily for 4 days. The results showed that the A. absinthium extract reversed the decrease in renal cell viability induced by cisplatin, whereas it decreased the reactive oxidative stress accumulation and apoptosis in LLC-PK1 cells. Shikimic acid also reversed the effect on cell viability but decreased oxidative stress and apoptosis in renal cells compared with the levels in the cisplatin-treated group. Furthermore, shikimic acid protected against kidney injury in cisplatin-treated mice by reducing serum creatinine levels. The protective effect of shikimic acid against cisplatin-mediated kidney injury was confirmed by the recovery of histological kidney injury in cisplatin-treated mice. To the best of our knowledge, this study is the first report on the nephroprotective effect of A. absinthium extract and its mechanism of action against cisplatin-induced renal injury.

Obesity is a primary factor provoking various chronic disorders, including cardiovascular disease, diabetes, and cancer, and causes the death of 2.8 million individuals each year. Diet, physical activity, medications, and surgery are the main therapies for overweightness and obesity. During weight loss therapy, a decrease in energy stores activates appetite signaling pathways under the regulation of neuropeptides, including anorexigenic [corticotropin-releasing hormone, proopiomelanocortin (POMC), cholecystokinin (CCK), and cocaine- and amphetamine-regulated transcript] and orexigenic [agouti-related protein (AgRP), neuropeptide Y (NPY), and melanin-concentrating hormone] neuropeptides, which increase food intake and lead to failure in attaining weight loss goals. Ginseng and ginsenosides reverse these signaling pathways by suppressing orexigenic neuropeptides (NPY and AgRP) and provoking anorexigenic neuropeptides (CCK and POMC), which prevent the increase in food intake. Moreover, the results of network pharmacology analysis have revealed that constituents of ginseng radix, including campesterol, beta-elemene, ginsenoside Rb1, biotin, and pantothenic acid, are highly correlated with neuropeptide genes that regulate energy balance and food intake, including ADIPOQ, NAMPT, UBL5, NUCB2, LEP, CCK, GAST, IGF1, RLN1, PENK, PDYN, and POMC. Based on previous studies and network pharmacology analysis data, ginseng and its compounds may be a potent source for obesity treatment by regulating neuropeptides associated with appetite.

Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called “Man HyungJa” in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.

Acer tegmentosum, a deciduous tree belonging to Aceraceae, has been used in traditional oriental medicine for treating hepatic disorders, such as hepatitis, cirrhosis, and liver cancer. We evaluated the estrogen-like effects of A. tegmentosum using an estrogen receptor (ER)-positive breast cancer cell line, namely MCF-7, to identify potential phytoestrogens and found that an aqueous extract of A. tegmentosum promoted cell proliferation in MCF-7 cells. Five phenolic compounds (1–5) were separated and identified from the active fraction using bioassay-guided fractionation of crude A. tegmentosum extract and phytochemical analysis. The chemical structures of the compounds were characterized as vanillic acid (1), 4-hydroxy-benzoic acid (2), syringic acid (3), isoscopoletin (4), and (E)-ferulic acid (5) based on the analysis of their nuclear magnetic resonance spectra and liquid chromatography-mass spectrometry data. All five compounds were evaluated using an E-screen assay for their estrogen-like effects on MCF-7 cells. Among the tested compounds, only 4-hydroxy-benzoic acid (2) promoted the proliferation of MCF-7 cells, which was mitigated by the ER antagonist, ICI 182,780. The mechanism underlying the estrogen-like effect of 4-hydroxy-benzoic acid (2) was evaluated via western blotting analysis to determine the expression levels of extracellular signal-regulated kinase (ERK), phosphoinositide 3-kinase (PI3K), serine/threonine kinase (AKT), and ERα. Our results demonstrated that 4-hydroxy-benzoic acid (2) induced the increase in the protein expression levels of p-ERK, p-AKT, p-PI3K, and p-Erα, concentration dependently. Collectively, these experimental results suggest that 4-hydroxy-benzoic acid (2) is responsible for the estrogen-like effects of A. tegmentosum and may potentially aid in the control of estrogenic effects during menopause.

Reactive oxygen species (ROS) are a major causative factor of inflammatory responses and extracellular matrix degradation. ROS also cause skin aging and diverse cutaneous lesions. Therefore, antioxidants that inhibit the generation of ROS may be beneficial in the relief of skin aging and diseases. We investigated the anti-skin aging effect of anthraquinones from cultures of Colletotrichum sp., an endophytic fungus isolated from Morus alba L. using human dermal fibroblasts (HDFs). We preferentially evaluated the preventive effects of anti-oxidative anthraquinones (1, 4) against the generation of ROS, nitric oxide (NO), and prostaglandins-E₂ (PGE₂). Among them, 1,3-dihydroxy-2,8-dimethoxy-6-methylanthraquinone (1) suppressed the generation of ROS, NO, and PGE₂ in tumor necrosis factor-alpha (TNF-α)-stimulated HDFs. Compound 1 reversed the TNF-induced increase in matrix metalloproteinase (MMP)-1 and a decrease in procollagen I α1 (COLIA1). It also suppressed inducible NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8, which upregulate inflammatory reactions. Mechanistically, compound 1 suppressed nuclear factor-κB, activator protein 1, and mitogen-activated protein kinases in TNF-α-stimulated HDFs. These results suggest that compound 1 may be beneficial for improving skin aging and diverse cutaneous lesions.