Plantago major L., commonly known as plantain, waybread, or dooryard plantain, is a versatile medicinal plant with multiple therapeutic applications. Traditionally, various parts of the plant have been formulated into syrups, drops, ointments, vaginal suppositories, gargles, and roasted preparations to treat diverse ailments, such as liver disorders, earaches, epilepsy, asthma, stomachaches, diarrhea, constipation, polymenorrhea, and uterine disorders. The plant contains clinically valuable bioactive compounds, including polysaccharides, flavonoids, lipids, iridoid glycosides, caffeic acid derivatives, terpenoids, alkaloids, and organic acids. These bioactive constituents are the primary contributors to the plant’s broad spectrum of biological activities, including antioxidant, anti-inflammatory, antibacterial, antidiarrheal, hepatoprotective, antiviral, antiphage, antinociceptive, antiulcerogenic, antigenotoxic, and immunomodulatory effects of the plant. This review comprehensively summarizes the phytochemical composition, traditional medicinal applications, and biological properties of this multifunctional medicinal plant.
Objective: To investigate the protective effects of gypenoside XVII (GP-17) against cisplatin-induced acute kidney injury and to elucidate whether its mechanism involves the activation of PINK1/Parkin-mediated mitophagy.
Methods: Sprague-Dawley rats were randomly divided into four groups: control, cisplatin, cisplatin + GP-17, and GP-17 alone. Cisplatin was administered intraperitoneally at 20 mg/kg to induce acute kidney injury, while GP-17 was given orally at 40 mg/kg/ day for 7 d. The levels of serum creatinine and blood urea nitrogen, superoxide dismutase activity, and malondialdehyde content were measured. Histopathological analysis and transmission electron microscopy were also performed to evaluate the effects of GP-17 on renal injury. Moreover, the expression of mitophagy-related proteins, including PINK1, Parkin, LC3, and p62, and the mRNA expression of inflammatory markers were determined by Western blot and quantitative RT-PCR assays. Furthermore, human renal tubular epithelial HK-2 cells were treated with cisplatin and GP-17, with or without PINK1 siRNA transfection. Cell viability, apoptosis, reactive oxygen species levels, mitochondrial membrane potential, and the protein expression associated with the PINK1/Parkin pathway were measured.
Results: In rats with cisplatin-induced acute kidney injury, GP-17 significantly ameliorated cisplatin-induced elevations in serum creatinine and blood urea nitrogen, attenuated tubular damage and mitochondrial ultrastructural injury, and reduced oxidative stress by increasing superoxide dismutase activity and decreasing malondialdehyde content. GP-17 further upregulated the protein levels of PINK1, Parkin, and LC3-II / I ratio while promoting p62 degradation, indicating enhanced mitophagic flux. In HK-2 cells, GP-17 (20 μM) co-treatment markedly attenuated cisplatin-induced cytotoxicity, apoptosis, reactive oxygen species overproduction, and mitochondrial depolarization. However, all these protective effects of GP-17 were completely abolished upon PINK1 knockdown.
Conclusions: GP-17 protects against cisplatin-induced nephrotoxicity by activating PINK1/Parkin-mediated mitophagy, which facilitates the clearance of damaged mitochondria, alleviates oxidative stress, and inhibits renal cell apoptosis. These findings identify GP-17 as a promising candidate for mitigating chemotherapy-induced acute kidney injury.
Objective: To investigate the efficacy and underlying mechanisms of standardized Salvia miltiorrhiza extract (SMEX) in alleviating menopausal symptoms using MCF-7 cells and an ovary-intact menopause mouse model resulting from hypothalamic-pituitary-ovarian axis aging.
Methods: Estrogen receptor (ER)-related molecular responses were first assessed in MCF-7 cells treated with SMEX. In vivo efficacy was then evaluated in 52-week-old female mice orally administered SMEX (50 or 100 mg/kg/day) or 17β-estradiol (E2) for 12 weeks. ER expression and downstream AKT/ERK signaling pathways in uterine tissues were determined. In addition, histological analysis of reproductive organs, assessment of serum lipid and hormone levels, neurotransmitter measurements, and behavioral tests were performed.
Results: SMEX upregulated ERα and ERβ expression and suppressed pS2 mRNA in MCF-7 cells, indicating selective ER modulation. In SMEX-treated mice, uterine ER expression and activation of the AKT and ERK pathways were significantly increased, leading to partial restoration of epithelial thickness and stratification in the oviduct and vagina. SMEX also significantly reduced serum low-density lipoprotein cholesterol levels and reversed menopausal alterations in the follicle-stimulating hormone/ luteinizing hormone ratio. Additionally, it elevated serotonin and norepinephrine levels in the pituitary, thereby alleviating depressionlike behavior.
Conclusions: SMEX modulates ER signaling and improves neurohormonal balance, effectively alleviating menopausal symptoms in both in vitro and in vivo models. This highlights its potential as a safe, natural alternative to hormone replacement therapy and as a promising functional ingredient in therapeutic natural products.
Objective: To assess the antitumor activity of the novel chitinase produced by fermented, isolated Trichoderma viride in a hepatocellular carcinoma (HCC) male rat model.
Methods: Diethyl-nitrosamine induction combined with ionizing radiation exposure was used to establish the HCC rat model. All rats were divided into 4 groups: the control group, the chitinase group, the HCC group, and the HCC + chitinase group. The antiproliferative effect of chitinase was evaluated in human HCC cells. The effect of chitinase in vivo on oxidative stress, endoplasmic reticulum stress chaperones, autophagy markers, PI3K/AKT/mTOR, AMPK pathway expression, and apoptotic indicators was determined and confirmed by histological examination.
Results: Chitinase significantly inhibited the viabilities of HepG2 cells. Moreover, in the Wistar male rat model of HCC, chitinase decreased ATP levels, modulated endoplasmic reticulum stress, mediated autophagy factors, and promoted apoptosis.
Conclusions: Chitinase might play a role in the apoptosis as well as autophagy pathways and may act as a potential tumor suppressor.