Phytomedicine最新文献

Background: The mosquito-borne pathogenic alphavirus known as Chikungunya virus (CHIKV) is becoming a greater hazard to public health, which causes thousands of cases annually in both rural and urban areas of many different nations throughout the world. Finding and creating new leads for the CHIKV virus is crucial because there are currently no effective medications or vaccinations against it. The non-structural protein 2 (nsP2) protease has emerged as a promising target for therapeutic intervention due to its crucial role in viral replication.

Purpose: This systematic review aims to evaluate recent advances in natural products as inhibitors of the CHIKV nsP2 protease, summarizing current research, identifying promising compounds, and highlighting gaps in the existing knowledge.

Study design: A comprehensive literature search was conducted between January 2006, and June 2024 using databases including PubMed, Scopus, Science Direct, and Google Scholar. Search terms included CHIKV, nsP2 protease, antivirals, natural products, phytochemicals, and inhibitors. Studies were selected based on predefined inclusion and exclusion criteria, focusing on original research articles examining natural products as inhibitors of CHIKV nsP2 protease.

Methods: Relevant studies were screened, and data were extracted regarding the source of natural compounds, methods of extraction, chemical structures, mechanisms of action, potency, and efficacy in inhibiting nsP2 protease or CHIKV replication.

Results: The review included 40 studies, revealing a variety of natural products and their derivatives with inhibitory effects on CHIKV nsP2 protease. Several compounds demonstrated promising inhibitory activity with EC50 values in the micromolar range. Mechanistic studies revealed diverse modes of action, including inhibition of protease activity or interference with viral replication processes.

Conclusion: Natural products have gained attention for their diverse chemical structures and bioactivities, offering a rich source of compounds with antiviral potential. We summarize the current knowledge on natural products derived from various sources including flavonoids, alkaloids, terpenoids, polyphenols, and some derivative compounds that have demonstrated inhibitory effects against CHIKV through different mechanisms of action. Overall, this systematic review underscores the importance of exploring natural products as promising candidates for the development of effective therapeutics against Chikungunya fever, particularly through targeting the nsP2 protease.

Background: Gut microbiota plays an important role in multiple human physiological processes and an imbalance in it, including the species, abundance, and metabolites can lead to diseases. These enteric microorganisms modulate immune homeostasis by presenting a myriad of antigenic determinants and microbial metabolites. Medicinal and food homologous (MFH) plants, edible herbal materials for both medicine and food, are important parts of Traditional Chinese Medicine (TCM). MFH plants have drawn much attention due to their strong biological activity and low toxicity. However, the interplay of MFH and gut microbiota in rebalancing the immune homeostasis in combating diseases needs systematic illumination.

Purpose: The review discusses the interaction between MFH and gut microbiota, including the effect of MFH on the major group of gut microbiota and the metabolic effect of gut microbiota on MFH. Moreover, how gut microbiota influences the immune system in terms of innate and adaptive immunity is addressed. Finally, the immunoregulatory mechanisms of MFH in regulation of host pathophysiology via gut microbiota are summarized.

Methods: Literature was searched, analyzed, and collected using databases, including PubMed, Web of Science, and Google Scholar using relevant keywords. The obtained articles were screened and summarized by the research content of MFH and gut microbiota in immune regulation.

Results: The review demonstrates the interaction between MFH and gut microbiota in disease prevention and treatment. Not only do the intestinal microorganisms and intestinal mucosa constitute an important immune barrier of the human body, but also lymphoid tissue and diffused immune cells within the mucosa participate in the response of innate immunity and adaptive immunity. MFH modulates immune regulation by affecting intestinal flora, helps maintain the balance of the immune system and interfere with the occurrence and development of a broad category of diseases.

Conclusion: Being absorbed from the gastrointestinal tract, MFH can have profound effects on gut microbiota. In turn, the gut microbiota also actively participate in the bioconversion of complex constituents from MFH, which could further influence their physiological and pharmacological properties. The review deepens the understanding of the relationship among MFH, gut microbiota, immune system, and human diseases and further promotes the progression of additional relevant research.

Background: Southern Schisandra is the dried and matured fruit of Schisandra sphenanthera Rehd. et Wils. in the family of Magnoliaceae; Traditional medicine reports that Schisandra sphenanthera has astringent and astringent properties, benefiting qi and promoting the production of body fluid, tranquilising the heart and calming the mind; it is clinically utilized for prolonged cough, thirst due to injury of the body fluid, internal heat and thirst, palpitation and insomnia, etc., and thirst belongs to the category of diabetes mellitus; the literature reports and the preliminary study of our team showed that Schisandra sphenanthera can be used to prevent and control diabetes mellitus.

Purpose: In the research, we investigated the mechanism of action of SDP against T2DM by integrating pharmacodynamics, endogenous metabolite assays and signalling pathways.

Materials and methods: UPLC-MS/MS was used to identify the chemical constituents. HPLC was utilized to determine the content of eight lignan-like components in SDP. A T2DM rat model was established by the combined induction of high-fat and high-sugar feed and STZ, and the mechanism of action of SDP on T2DM was investigated by using biochemical indices, Western blot analysis of protein expression, mRNA expression, immunohistochemistry and endogenous metabolites.

Results: The chemical components in SDP were determined by UPLC-MS/MS and HPLC, and biochemical indicators determined that SDP has the effects of lowering blood glucose, anti-glycolipid metabolism, and anti-oxidative stress, and is able to restore pathological damage in the liver and pancreas, activate the PI3K/AKT, AMPK/mTOR, and sweetness receptor signalling pathways, restore the sweetness receptor mRNAs, and modulate the urinary compounds such as malic acid, γ-aminobutyric acid, leucine, N-acetylaspartic acid and other compounds thereby achieving the therapeutic effect of T2DM.

Conclusion: SDP can ameliorate diabetes-induced symptoms related to elevated blood glucose, dyslipidaemia, elevated fasting insulin levels and impaired glucose tolerance in rats; the anti-T2DM of SDP may be through the regulation of the sweet taste receptor pathway, the PI3K/AKT/mTOR and the AMPK/mTOR signalling pathway, which leads to the development of a normal level and exerts an antidiabetic effect.

Background: Cardiovascular diseases (CVDs) are the leading causes of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors.

Purpose: This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies.

Method: This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to.

Results: Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function.

Conclusion: We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD.

Background: Traditional Chinese herbal medicines (TCMs) have become increasingly integrated into global healthcare systems, often used alongside conventional pharmaceuticals. While TCMs offer therapeutic benefits, their concomitant use with other medications raises concerns over cutaneous adverse drug reactions (CADRs). Despite the widespread use of TCMs, large-scale studies examining their safety in combination with antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) remain limited.

Objective: This study aimed to analyze the frequency and severity of CADRs associated with TCMs, focusing on their interactions with antibiotics and NSAIDs in a comprehensive dataset spanning over 15 years in China.

Methods: We retrospectively reviewed clinical data from over 1.8 million patient visits annually between 2007 and 2022. Both mild and severe CADRs (SCARs) associated with TCMs, antibiotics, and NSAIDs were evaluated.

Results: While used in combination with antibiotics or NSAIDs, TCMs did not significantly increase the incidence of SCARs, although TCMs, antibiotics, or NSAIDs accounted for a proportion of CADRs. In contrast, the combination of antibiotics with NSAIDs showed a higher frequency of SCARs compared to monotherapy. These results suggest that TCMs have a favorable safety profile in multi-drug regimens, but careful monitoring is essential, particularly in multi-drug therapies involving conventional medications.

Conclusion: This groundbreaking study provides unprecedented insights into the role of TCMs in CADRs, highlighting their potential for safer integration into multi-drug regimens. Although TCMs did not exacerbate the risk of severe reactions when combined with antibiotics or NSAIDs, vigilance in drug safety protocols remains crucial. These findings support the cautious and well-regulated use of TCMs within broader healthcare frameworks, promoting their safe integration alongside conventional therapies.

Background: Traditional Chinese medicine offers unique and valuable resources for the exploration of novel approaches to disease treatment. Panaxadiol, an active compound derived from the transformation of ginsenosides. It has a variety of pharmacological activities. However, there is a lack of research regarding its effects on Parkinson's disease (PD).

Purpose and study design: This study investigates the activity and mechanism of panaxadiol in the treatment of PD both in vivo and in vitro. In addition, a new method has been developed to extract panaxadiol.

Results: The results showed that in vitro, panaxadiol can reduce the viability and cytotoxicity of BV2 cells induced by LPS, and inhibit the production of pro-inflammatory factors through the TLR4/MyD88/NF-κB pathway. In vivo, panaxadiol can improve motor and intestinal dysfunction in PD mice and repair the loss of DA neurons. Further studies have shown that panaxadiol treatment alleviates damage to the blood-brain barrier (BBB), inhibits neuroinflammation in the substantia nigra (SN), and further reduces damage to DA neurons. Subsequently, it was found that panaxadiol alleviated peripheral inflammation and significantly restored the intestinal microbial community. Further mechanistic studies found that panaxadiol treatment inhibited the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products in the SN. In addition, Additionally, the response surface method was employed to identify the optimal conditions for extracting panaxadiol using a deep eutectic solvent (NADES).

Conclusion: In summary, this study has found for the first time that panaxadiol can effectively improve the symptoms of PD by regulating neuroinflammation, repairing the BBB, and gut microbiota. Meanwhile, adopting a green extraction process significantly increases the content of panaxadiol, providing a new direction for the development of PD candidate drugs.

Background: Phillygenin (PHI), a main bioactive compound found in the fruit of Forsythia suspensa, exhibits antiviral, antioxidant, anti-inflammatory, and antihypertensive activities. However, the molecular mechanisms underlying its effects on diabetic nephropathy (DN) remain unclear.

Purpose: To evaluate the therapeutic effects of PHI on DN and elucidate the molecular mechanisms involved.

Methods: Cell viability assays and RNA-seq analyses were performed to identify potential mechanisms through which PHI regulates HG-induced MPCs. The therapeutic efficacy of PHI was assessed in both DN cells and mouse models. Cytokine levels were measured using ELISA, while the expression levels of key signaling pathways, including TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β along with downstream effectors were analyzed via immunoblotting, immunofluorescence, and immunohistochemical staining.

Results: PHI inhibited inflammatory responses and alleviated apoptosis by reducing the expression levels of IL-6, TNF-α, IL-1β, TLR4, MyD88, NF-κB, and cleaved caspase-3, while enhancing the phosphorylation of PI3K, AKT, GSK3β (Ser9), and pro-caspase-3 in MPCs under HG conditions in vitro. Additionally, in vivo experiments demonstrated that treatment with PHI (50 mg/kg) in db/db mice effectively improved renal function and attenuated kidney injury by reducing the urinary albumin-to-creatinine ratio (UACR), mitigating podocyte apoptosis, and inhibiting inflammatory via modulation of the TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways.

Conclusion: PHI inhibits inflammation and apoptosis in vitro and alleviates diabetic kidney injury in db/db mice by interfering TLR4/MyD88/NF-κB and PI3K/AKT/GSK3β signaling pathways. Thus, this study reveals for the first time that PHI is a potential novel therapeutic agent for DN.

Background: The primary adverse effect of chemotherapy drugs is the induction of spermatogenic disorders. Schisandra chinensis (Turcz) Baill. have been preliminarily shown to have a significant ameliorative in spermatogenic disorders. Nevertheless, there are relatively few studies on non-medicinal parts such as stems of S. chinensis, which have good therapeutic potential for side effects caused by cisplatin. Up to now, a total of 238 compounds have been isolated and identified from the vine stem of S. chinensi. The main components are lignans, polysaccharides, volatile oils, and organic acids. Therefore, the development of S. chinensis stem as a source of a novel chemotherapy drug protector is of great significance.

Methods: In the present study, we explored the protective effect of the stem extract of S. chinensis (SCE) against cisplatin-induced spermatogenic disorders and its possible molecular mechanisms in vitro and in vivo. The network pharmacology was used to predict the targets that may act on spermatogenic disorders. Mice were injected intraperitoneally with cisplatin at 2 mg/kg for 7 days to induce spermatogenic disorders. SCE (75, 150, and 300 mg/kg) was administered to mice by gavage for 21 days. TM3 cells were treated with Schisandrol B (Sol B) (0.5, 1, and 2 µM) in the presence or absence of cisplatin (40 µM), and then cell viability, oxidative stress, apoptosis, and mitochondrial function were evaluated.

Results: 16 constituents and target proteins were predicted to have possible effects on spermatogenic disorders by network pharmacology. Both in vivo and in vitro experiments showed a favorable protective effect of SCE against cisplatin-induced spermatogenic disorders. Sol B might as the major chemical component is responsibility for the protective effect. The mechanism may involve the regulation of Nrf2HO-1 protein, PI3KAkt, apoptosis, and MAPK signaling pathway to modulate 17βHSD, cycp450, Star and other crucial proteins in the testosterone synthesis pathway. Ultimately, this regulatory process aims to ameliorate the disruption of sex hormone secretion by cisplatin.

Conclusion: These results indicated that the lignans in SCE could effectively improve the spermatogenesis barrier caused by cisplatin. These findings provided a theoretical basis for the development of non-medicinal parts of S. chinensis, and laid a foundation for improving spermatogenesis disorders caused by chemotherapy drugs.

Background: The global incidence of calcium oxalate (CaOx) kidney stones is rising, and effective treatments remain limited. Luteolin (Lut), a naturally flavonoid present in several plants, is recognized for its anti-inflammatory, anti-injury, and neuroprotective effects. However, its effects on CaOx kidney stone formation and the associated kidney damage are still unknown.

Objective: Our study seeks to explore the therapeutic impact of Lut on kidney injury and renal fibrosis caused by CaOx crystal and to elucidate the underlying mechanisms.

Methods: CaOx stone models were established in mice via intraperitoneal injection of glyoxylate (Gly, 100 mg/kg) for 12 days. Lut (50 mg/kg or 100 mg/kg) was administered intraperitoneally 7 days before and with the period of Gly treatment. Kidney function and histopathology changes in renal tissues were assessed. RNA sequencing was used to explore potential mechanisms between the model and Lut treatment groups. Molecular docking simulations evaluated the interaction between Lut and the downstream target Nr4a1. Moreover, Nr4a1 knockout mice and knockdown plasmids were used to validate the mechanism of Lut in the treatment of CaOx crystal-induced kidney injury.

Results: Lut significantly mitigated kidney injury and renal fibrosis induced by CaOx crystal, as evidenced by improved kidney function, histopathology staining and Western blot analysis. Lut treatment also significantly inhibited lipid peroxidation and mitochondrial injury. In vitro experiments further demonstrated that Lut treatment alleviated injury and fibrosis in HK-2 cells. Mechanistically, RNA sequencing and molecular docking simulations indicated that Lut binds to Nr4a1 to regulate ferroptosis, thereby alleviating kidney injury induced by CaOx crystal. Overexpression of Nr4a1 negated Lut's beneficial effects, whereas Nr4a1 knockout exhibited a protective effect against kidney injury.

Conclusion: Lut exerts its protective effects by inhibiting ferroptosis via targeting Nr4a1-Slc7a11-GPX4 pathway, alleviating kidney injury and renal fibrosis caused by CaOx crystal deposition.