Phytotherapy Research最新文献

Bergapten (BP) is a plant-derived furocoumarin that has a wide range of pharmacological effects. BP serves as a candidate amplifier in phototherapy against skin inflammation, such as psoriasis and atopic dermatitis. However, the anti-inflammatory role of BP remains elusive. We utilized IL-17A-stimulated keratinocyte line and imiquimod-challenged BALB/c mice to imitate psoriasis-like inflammation. Inflammatory phenotypes were determined by expressions of inflammatory genes and cytokines, histopathological changes and activities of nuclear factor-κB (NF-κB) pathway. An RNA-seq analysis of rodent skin was performed to explore possible mechanism lying behind. SiRNAs and antagonist (TMS) against cytochrome P450 family 1 subfamily B member 1 (CYP1B1) were subsequently used to determine the role of CYP1B1 in psoriasis pathogenesis in vitro and in vivo. Overexpression of CYP1B1 with lentivirus further validate therapeutic effect of BP. BP significantly suppressed activation of the NF-κB pathway by inhibiting p65 phosphorylation and improved the inflammatory phenotype both in vitro and in vivo. We revealed the key role of CYP1B1 in regulating the activation of the NF-κB signaling pathway. Knock-down with siRNAs significantly reduce the expression of inflammatory genes and cytokines. An intraperitoneal injection of TMS partially remediated IMQ-induced inflammation, mainly in terms of skin thickness. Overexpression of Cyp1b1 led to increased expression of the CYP1B1 protein and rescued the therapeutic effect of BP in vitro. This study revealed that BP suppressed expression of Cyp1b1 in keratinocytes and inhibited the activation of NF-κB signaling pathway by blocking the phosphorylation of p65.

Atopic dermatitis (AD) is a common inflammatory dermatitis of the skin and poses therapeutic challenges due to the adverse reactions and high costs associated with available treatments. In Eastern Asian countries, a plethora of herbal remedies is extensively employed for the alleviation of AD. Many of these botanicals are renowned for their formidable anti-inflammatory properties, contributing to AD management. Chinese herbal medicine (CHM) and its active ingredients exhibit both prophylactic and therapeutic promise against AD by modulating inflammatory response, orchestrating immune system functions, and enhancing antioxidant activities. A comprehensive exploration of the underlying mechanisms involved in CHM treatment can enhance the comprehension of AD pathogenesis and facilitate the development of innovative drugs for AD. This study aims to elucidate the signaling pathways and potential targets implicated in CHM-based treatment of AD, providing a systematic theoretical framework for its application in therapy while serving as a valuable reference for developing more effective and safer AD therapeutic agents.

With the development of medicine and chemistry, an increasing number of plant-derived medicines have been shown to exert beneficial therapeutic on the treatment of various physical and psychological diseases. In particular, by using physical chemistry methods, we are able to examine the chemical components of plants and the effects of these substances on the human body. Muscle atrophy (MA) is characterized by decreased muscle mass and function, is caused by multiple factors and severely affects the quality of life of patients. The multifactorial and complex pathogenesis of MA hinders drug research and disease treatment. However, phytotherapy has achieved significant results in the treatment of MA. We searched PubMed and the Web of Science for articles related to plant-derived substances and muscle atrophy. After applying exclusion and inclusion criteria, 166 and 79 articles met the inclusion criteria, respectively. A total of 173 articles were included in the study after excluding duplicates. The important role of phytoactives such as curcumin, resveratrol, and ginsenosides in the treatment of MA (e.g., maintaining a positive nitrogen balance in muscles and exerting anti-inflammatory and antioxidant effects) has been extensively studied. Unfortunately, MA dose not have to a single cause, and each cause has its own unique mechanism of injury. This review focuses on the therapeutic mechanisms of active plant components in MA and provides insights into the personalized treatment of MA.

A high-fat diet (HFD) is often associated with hepatic lipid metabolism disorders, leading to dysfunction in multiple body systems. Ginsenosides derived from Panax ginseng have been reported to possess potential effects in ameliorating lipid metabolism disorders; however, their underlying mechanisms remain insufficiently explored. This study aims to investigate the bioactivities of ginsenosides in combating lipid metabolism disorders and obesity, with a focus on their mechanisms involving the cholesterol metabolism signaling pathway and gut microbiota. Our results demonstrated that ginsenoside treatment significantly reduced overall body weight, body weight changes, liver weight, and eWAT weight, as well as alleviated hepatic steatosis and dyslipidemia in HFD-fed rats, without affecting food intake. These effects were dose-dependent. Furthermore, 16S rRNA sequencing revealed that ginsenosides significantly increased the relative abundance of Akkermansia muciniphila, Blautia, Eisenbergiella, Clostridium clusters XI, XVIII, and III, while decreasing the relative abundance of Clostridium subcluster XIVa and Dorea. In addition, ginsenoside treatment significantly regulated the expression of hepatic genes and proteins involved in the cholesterol metabolism signaling pathway (FXR, CYP7A1, CYP7B1, CYP27A1, ABCG5, ABCG8, Insig2, and Dhcr7), potentially inhibiting hepatic cholesterol biosynthesis while promoting cholesterol transport to HDL and its excretion via bile and feces. Notably, levels of 7-dehydrocholesterol (7-DHC) and 27-hydroxycholesterol (27-OHC) were reduced, while 5β,6β-epoxycholesterol (5,6β-epoxy) levels were elevated following ginsenoside treatment, indicating significant modulation of oxysterols by ginsenosides. Moreover, bile acid enterohepatic circulation was regulated through the enhancement of hepatic FXR-CYP7A1 signaling and intestinal FXR-FGF15 signaling in HFD-fed rats treated with ginsenosides, which was closely linked to gut microbiota composition. Collectively, our findings suggest that ginsenosides alleviate hepatic lipid metabolism disorders by modulating gut microbiota and the cholesterol metabolism signaling pathway in HFD-fed rats.

Pulmonary hypertension (PH) is a severe pulmonary vascular disease characterized by poor clinical outcomes and limited therapeutic options. Celastrol (CEL), a natural product derived from Tripterygium wilfordii Hook F, has shown therapeutic potential in PH models, although its mechanisms are not fully understood. This study aims to investigate the role of CEL in PH and explore its potential underlying mechanisms. This study investigates the role of CEL in PH and explores its underlying mechanisms. We evaluated the effects of CEL in a chronic hypoxia-induced PH rat model and hypoxia-stimulated human pulmonary arterial smooth muscle cells (HPASMCs). Bioinformatics and network pharmacology were employed to identify potential targets and pathways, which were then validated through mechanistic and functional analyses. CEL significantly reduced right ventricular systolic pressure, hypertrophy, fibrosis, and dysfunction in hypoxia-induced PH rats. It also decreased proliferating cell nuclear antigen expression and promoted apoptosis in pulmonary arterioles. Our findings suggest that CEL's therapeutic effects are mediated through the modulation of phosphodiesterase 5 (PDE5) and the activation of the cGMP-PKG signaling pathway. In HPASMCs, CEL treatment mirrored the in vivo results, and PDE5 overexpression negated CEL's antiproliferative, antimigratory, and pro-apoptotic effects. CEL ameliorates pulmonary vascular remodeling and right ventricular dysfunction in PH, potentially through the PDE5-cGMP-PKG signaling pathway. These findings position CEL as a promising candidate for PH therapy.

The human body gets exposed to a variety of toxins intentionally or unintentionally on a regular basis from sources such as air, water, food, and soil. Certain toxins can be synthetic, while some are biological. The toxins affect the various parts of the body by activating numerous pro-inflammatory markers, like oxidative stresses, that tend to disturb the normal function of the organs ultimately. Nowadays, people use different types of herbal treatments, viz., herbal drinks that contain different spices for detoxification of their bodies. One such example is turmeric, the most commonly available spice in the kitchen and used across all kinds of households. Turmeric contains curcumin, which is a natural polyphenol. Curcumin is a medicinal compound with different biological activities, such as antioxidant, antineoplastic, anti-inflammatory, and antibacterial. Hence, this review gives a comprehensive insight into the promising potential of curcumin in the detoxification of heavy metals, carbon tetrachloride, drugs, alcohol, acrylamide, mycotoxins, nicotine, and plastics. The review encompasses diverse animal-based studies portraying curcumin's role in nullifying the different toxic effects in various organs of the body (especially the liver, kidney, testicles, and brain) by enhancing defensive signaling pathways, improving antioxidant enzyme levels, inhibiting pro-inflammatory markers activities and so on. Furthermore, this review also argues over curcumin's safety assessment for its utilization as a detoxifying agent.

This narrative review describes the provenance and chemical composition of Vitex agnus-castus, as well as the currently available knowledge concerning its action. To search the related articles, Cochrane Library, PubMed, Web of Science, SCOPUS databases between the years 1995 and 2024, and the keywords "Vitex," "review," "fertility," "ovarian" and "mechanisms" were used in various combinations. The data listed in this review demonstrate that Vitex agnus-castus and its constituents (isoflavones and essential oils) affect a number of physiological actions via multiple extra- and intracellular mechanisms of action. This makes it an efficient drug in both traditional and modern medicine for the treatment of a number of illnesses. The main described target of Vitex agnus-castus is female reproduction. It can up-regulate ovarian cycle and fecundity via a wide spectrum of mediators from hypothalamic, pituitary and ovarian hormones up to intracellular regulators of proliferation, apoptosis, oxidation and dopamine receptors. These effects determine its potential action as protector and medicine against a number of female reproductive disorders and reproduction-related health problems including menstrual disorders, premenstrual syndrome, cyclic mastalgia, corpus luteum insufficiency, abnormal production of progesterone and prolactin, low fertility and infertility, hyperandrogenism and polycystic ovarian syndrome. Nevertheless, further high-quality studies are needed to firmly establish the biological and clinical efficacy of this plant.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, but effective therapeutic drugs are still lacking. Dihydrotanshinone I (DHTS), a natural product isolated from Salvia miltiorrhiza, has been shown to have ameliorative effects on NAFLD. The aim of this study was to investigate the hepatoprotective effect of DHTS on NAFLD and its mechanism. A model of NAFLD and DHTS treatment was established using a Western diet to observe the effect of DHTS on NAFLD, which were detected by immunohistochemical, immunofluorescence, and other experiments. The mechanism was further explored by constructing immune responsive gene 1 (IRG1) knockout mice, RNA sequence, and molecular docking. The results revealed that DHTS significantly improved diet-induced metabolic disorders in mice, notably alleviating liver inflammation, oxidative stress, and fibrosis. Further analysis revealed that the intervention of DHTS was associated with the activation of IRG1. Subsequent experiments confirmed that IRG1 gene deletion reversed the above protective effects of DHTS in NAFLD. Mechanistically, DHTS enhanced the antioxidant nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway through IRG1/itaconate and blocked the oxidative stress response in the liver. In addition, DHTS also inhibited the activation of NACHT-, leucine-rich repeat (LRR)-, and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome via IRG1/itaconate, blocking the inflammatory amplification effect in the liver. The study suggests that DHTS may be a potential drug for the treatment of NAFLD, which exerts protective regulatory effects mainly through the IRG1/itaconate molecular pathway.

Alzheimer's disease (AD) is a type of neurodegenerative illness in which β-amyloid (Aβ) and tau protein accumulate in neurons in the form of tangles. The pathophysiological pathway of AD consists of Aβ-amyloid peptides, tau proteins, and oxidative stress in neurons and increased neuro-inflammatory response. Food and Drug Administration in the United States has authorized various drugs for the effective treatment of AD, which include galantamine, rivastigmine, donepezil, memantine, sodium oligomannate, lecanemab, and aducanumab. The major disadvantage of these drugs is that they only provide "symptomatic" relief. They are most effective in the early stages or for mild to moderate cases of the disease, but are not suitable for long-term use. Besides conventional therapies, phytochemicals have the potential to stop the progression of AD. According to research, the use of potential phytochemicals against AD has gained attention due to their potent anti-inflammatory, antioxidant, anti-hyperphosphorylation of the tau protein, metal chelation, and anti-amyloid properties. This study seeks to provide an up-to-date compilation of the most current and promising breakthroughs in AD therapy using phytochemicals. It could be concluded that phytochemicals light serve as an effective therapy for AD. However, more mechanistic investigations are needed to determine the clinical implications of phytochemicals in AD treatment.

Chronic migraine (CM) is a disabling neurological disease. Astragaloside IV (AS-IV), a natural product derived from Astragalus membranaceus, shows great potential in treating chronic pain by relieving inflammation and oxidative stress. This study aimed to investigate the effects and mechanisms of action of AS-IV on CM. An inflammatory soup comprising histamine, bradykinin, serotonin, and prostaglandin E2 was used to establish a CM rat model, while lipopolysaccharide was applied to induce an inflammatory response in primary astrocytes. Pain threshold measurements were used to evaluate nociceptive hypersensitivity, while qPCR and Western blotting were applied to detect inflammatory indicators and synaptic protein expression, and Golgi-Cox staining was applied to observe dendritic spine density, while transmission electron microscopy was used to observe synaptic ultrastructure. Mitochondrial function and oxidative stress were assessed using JC-1 staining, Mitotracker staining, reactive oxygen species (ROS) quantification, and glutathione content. AS-IV pretreatment alleviated central sensitization and ameliorated astrocyte activation and neuroinflammation. AS-IV pretreatment alleviated mitochondrial dysfunction in vitro, and reduced the nuclear translocation of NF-κB and the production of IL-1β, which were reversed by ROS scavengers in vitro or mitochondrial respiratory chain disruptors in vivo. Our study indicates that AS-IV can inhibit neuroinflammation by alleviating astrocyte mitochondrial dysfunction to mitigate central sensitization in CM, thereby providing an experimental basis for AS-IV and A. membranaceus in CM prevention and treatment.