Phytotherapy Research最新文献

With the passage of time, people step toward old age and become more prone to several diseases associated with the age. One such is Alzheimer's disease (AD) which results into neuronal damage and dementia with the progression of age. The existing therapeutics has been hindered by various enkindles like less eminent between remote populations, affordability issues and toxicity profiles. Moreover, lack of suitable therapeutic option further worsens the quality of life in older population. Developing an efficient therapeutic intervention to cure AD is still a challenge for medical fraternity. Recently, alternative approaches attain the attention of researchers to focus on plant-based therapy in mitigating AD. In this context, flavonoids gained centrality as a feasible treatment in modifying various neurological deficits. This review mainly focuses on the pathological facets and economic burden of AD. Furthermore, we have explored the possible mechanism of flavonoids with the preclinical and clinical aspects for curing AD. Flavonoids being potential therapeutic, target the pathogenic factors of AD such as oxidative stress, inflammation, metal toxicity, Aβ accumulation, modulate neurotransmission and insulin signaling. In this review, we emphasized on potential neuroprotective effects of flavonoids in AD pathology, with focus on both experimental and clinical findings. While preclinical studies suggest promising therapeutic benefits, clinical data remains limited and inconclusive. Thus, further high-quality clinical trials are necessary to validate the efficacy of flavonoids in AD. The study aim is to promote the plant-based therapies and encourage people to add flavonoids to regular diet to avail the beneficial effects in preventive therapy for AD.

The activation of neural stem cells (NSCs) residing in the subventricular zone (SVZ) and dentate gyrus (DG) has been shown to promote the restoration of damaged brain tissues. Ginsenoside Rb3 (Rb3) is a bioactive substance known for its pharmacological properties in treating neurological disorders. This study investigated the effects of Rb3 on neural regeneration following ischaemic stroke (IS) and the underlying mechanisms involved. Male C57BL/6 mice were utilized and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, Rb3 was administered through intraperitoneal (i.p.) injection for either 7 or 28 days. The promotion of Rb3 on regenerative neurogenesis was detected by immunofluorescence staining. NSCs were pretreated with different concentrations of Rb3 for 24 h before oxygen-glucose deprivation/reoxygenation (OGD/R) exposure. Afterward, immunofluorescence staining and flow cytometry were used to detect the migration and proliferation of Rb3 in OGD/R-induced NSCs. Furthermore, Adeno-associated virus (AAV) transduction experiments, siRNA transfection experiments, gene knockout experiments, targeted metabolomics analysis, molecular dynamics simulation, cellular thermal shift assay (CETSA), and drug affinity responsive target stability (DARTS) assays were used to explore the promotion and mechanism of Rb3 on regenerative neurogenesis following IS. Rb3 promoted Opa1-mediated NSCs migration and proliferation. Knockdown of Opa1 blunted the above-promoting effects of Rb3 in both the brains of ischemia-reperfusion (I/R)-treated mice and OGD/R-treated NSCs. Mechanistically, targeted metabolomics, molecular dynamics, molecular docking, CETAS, and DARTS experiments showed that Rb3 promoted Opa1-mediated neural regeneration required the activation of Ido1 and that Ido1 served as a direct target of Rb3 to repair I/R injury. Moreover, studies in siRNA-mediated knockdown and KO mice revealed that inhibition of Ido1 attenuated the enhancing effect of Rb3 on mitochondrial fusion. Our study provides novel evidence that Rb3 promotes neurogenesis through an Ido1/Opa1-mediated pathway involving the interaction between Rb3 and Ido1, leading to improved long-term neurological function. These results indicate that Rb3 or other mitochondrial fusion promoters could be a potential neurorestorative strategy for regenerative neurogenesis following IS.

Curcumin, a well-known bioactive component, has profound effects against colon cancer. However, the limitations are poor systemic absorption, off-target distribution, chemical instability, short half-life, and less concentration reaching tumor tissues. Several drug delivery systems have been evaluated so far to deliver effective concentrations of curcumin to the malignant tissues. This review aims to explore the role of smart polymers in overcoming limitations in curcumin delivery against colon cancer. Literature of the past 10 years was collected from Scopus, PubMed/Medline, Google Scholar, and Science Direct using specific keywords. Several preclinical and clinical studies of curcumin against colon cancer with the inclusion of smart polymers were screened using keywords like "FDA-approved biomaterials," "stimuli-responsive polymer," "smart biomaterial," and so forth. Smart polymer phrase is used to describe all the mentioned polymers in the manuscript. Stimuli-responsive polymers, including poly-lactic-co-glycolic acid (PLGA), polyethylene glycol (PEG), Eudragit, cyclodextrin, and chitosan, have emerged as promising candidates for curcumin delivery against colon cancer. These polymers facilitate controlled drug release in response to stimuli such as temperature, pH, and enzymes, while offering biocompatibility, biodegradability, and safety. The five selected FDA-approved smart polymers exhibit the potential for enhancing curcumin delivery against colon cancer.

Glioma is recognized as one of the most lethal and aggressive brain tumors. Although the standard-of-care treatment for glioblastoma (GBM) involves maximal surgical resection and temozolomide (TMZ) chemotherapy, the discovery of novel anti-tumor agents from nature sources is an effective strategy for glioma treatment. In this study, we conducted a screening process to identify the bisindole alkaloid melodinine J (MDJ) from Melodinus tenuicaudatus. We assessed its potency in overcoming TMZ resistance in patient-derived recurrent glioma strains, TMZ-resistant cell lines, and nude mouse tumor models of glioma cells. Our results first indicated that MDJ effectively inhibited malignancy and stimulated apoptosis in glioma. Mechanistic studies revealed that MDJ triggered deadly mitochondrial dysfunction and apoptosis by disrupting cross-organellar communication between the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). We also showed that high levels of TMX1 may promote malignancy of glioma by ER-mitochondria communications, bioenergetics efficiency, and tumor growth. Overall, our study proved that MDJ interfered the function of TMX1-mediated MAM networks, thereby overcoming the proliferation and chemo-resistance of glioma cells.

In recent years, marine natural products (MNPs) have emerged as crucial sources of lead compounds for the advancement of anti-inflammatory drugs due to their abundant diversity, complexity, and distinctiveness. Inflammatory microenvironments (IMEs) are pervasive pathological features in the etiology of various chronic diseases, referring to the localized milieu or ecosystem where inflammatory responses occur, and they play a pivotal role in the onset and progression of inflammatory diseases. Uncontrolled IMEs can lead to dysregulation of inflammatory mediators within signaling pathways, thereby exerting detrimental effects on human health and even contributing to the development of inflammatory diseases such as cancer. Currently, inflammation treatment predominantly relies on chemical drugs. Nevertheless, these existing therapies are constrained by their numerous side effects and slow remission of symptoms. Consequently, there is an urgent need for the discovery and development of new drugs that exhibit minimal side effects while exerting potent anti-inflammatory effects. This article extensively explored the activities and mechanisms of MNPs (covering studies from 2010 to 2024) regulating key signaling pathways and inflammatory mediators in the IME, which establishes a theoretical basis for the further development of anti-inflammatory drugs.

Acute hepatic injury (AHI) is associated with poor prognosis in sepsis patient; however, to date, no specific therapeutic approach has been established for this disease. Therefore, we aimed to explore the effects and action mechanisms of Astragaloside IV (AS) on AHI. C57BL/6 mice, RAW264.7 cells, and bone marrow-derived macrophages were used in this study. Sepsis-associated AHI model mice were established using lipopolysaccharide + D-galactosamine. Pathological examination of liver tissues and serum alanine aminotransferase/aspartate aminotransferase was performed to evaluate the liver function. Moreover, inflammatory cytokine levels, proportion of M1/M2 macrophages and their marker levels, and cell pyroptosis-related indicator levels were determined in the liver of the AHI model mice with or without AS treatment. AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) expression was determined after AS treatment. Additionally, inflammatory cytokine levels, liver injury, and macrophage polarization were evaluated after inhibiting the AMPK/SIRT1 pathway. AS alleviated lipopolysaccharide + D-galactosamine-induced AHI and inhibited inflammatory reactions in the blood and liver of mice. AS also promoted the M1-to-M2 phenotypic transformation of macrophages in the liver of AHI model mice and in vitro, thereby decreasing the pro-inflammatory cytokine levels and increasing the anti-inflammatory cytokine levels. AS increased AMPK and SIRT1 levels in the liver and macrophages. Furthermore, AS improved liver injury by elevating the expression of the AMPK/SIRT1 signaling pathway and inhibiting pyroptosis in macrophages. Overall, AS alleviated AHI by promoting M1-to-M2 macrophage transformation and inhibiting macrophage pyroptosis via activation of the AMPK/SIRT1 signaling pathway.

Dengue virus (DENV) continues to pose a significant global health challenge, causing diseases such as dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. While efforts in vaccine development and antiviral drug discovery are ongoing, effective therapeutic options remain limited. In this review, we highlight natural compounds and the analogs that demonstrated antiviral activity against DENV in in vitro and in vivo studies. Specifically, these studies examine alkaloids, phenolic acids, phenols, flavonoids, terpenoids, and glycosides which have shown potential in inhibiting DENV entry, replication, and reducing the cytokine storm. By focusing on these bioactive compounds and the analogs, a comprehensive overview of their promising roles is provided to advance therapeutic strategies for combating DENV infection.

Psoriasis is a noncontagious, autoimmune chronic inflammatory disease with an unknown root cause. It is classified as a multifactorial and chronic skin disorder that also affects the immune system and is genetic. Environmental factors such as stress, infections, and injuries all play an important role in the disease's development. Although there is no cure for this disease, topical, oral, and systemic whole-body treatments are available to relieve symptoms. Several plants and phytochemicals which have been found effective in the management of the psoriasis experimentally (preclinical and clinical). These plants/phytochemicals have applications in topical, oral, and systemic treatments. Traditionally, some of the plants have been utilized as the primary treatment, including their extracts and/or phytochemicals, for individuals with moderate to severe psoriasis (due to fewer side effects), while phototherapy is generally reserved for more advanced cases. This report describes various plants and phytochemicals that have been found to be effective against psoriasis in in vitro, preclinical, and clinical studies. This review summarizes the key findings from experimental studies on various pathological aspects of psoriasis and may be useful, effective, and informative for future research.

Non-alcoholic steatohepatitis (NASH) has no effective treatment drug. Our previous study initially found that artemether (Art) treatment significantly attenuates NSAH by regulating liver lipid metabolism. This study further elucidates new mechanisms of Art in improving liver inflammation and provides evidence for drug repurposing. Herein, we utilized HFHF diet-induced animal model and macrophage models to detect the mechanisms of Art in NASH. We confirmed that Art significantly reduced hepatic steatosis, injury, and fibrosis in a high-fat high-fructose (HFHF) diet-induced animal model. Art significantly suppressed the activation of inflammatory macrophages and secretion of pro-inflammatory cytokine (IL-1β) by reducing serum double-stranded DNA (dsDNA) levels and triggering the AIM2/Caspase-1/GSDMD signaling in vivo. dsDNA-induced Caspase-1 and PI-positive cells pyroptosis, AIM2 inflammasome activation, IL-1β, and IL-18 secretion increase were inhibited by Art in vitro. Furthermore, we found Art effectively suppressed mitochondrial DNA (mtDNA), a typical form of dsDNA, released from free fatty acid (FFA)-stressed hepatocytes, which further inhibited AIM2 inflammasome mediated-pyroptosis through decreasing the cleavage of Caspase-1/GSDMD/IL-1β. Moreover, inhibition of the AIM2 gene partly reversed the inhibitory effect of Art on macrophage pyroptosis. Impaired mitochondrial structure and function were confirmed in FFA-stressed hepatocytes and the HFHF-diet-induced NASH mouse model, which was reversed by Art treatment. The present study provides evidence for Art as a potential anti-pyroptosis therapeutic agent for NASH treatment.

The most prevalent chronic liver disease for which there is currently no proven treatment is non-alcoholic fatty liver disease (NAFLD). An incomplete understanding of the underlying mechanisms of NAFLD may be the cause. The onset and development of this illness appear to be influenced by problems with lipid metabolism, insulin resistance, oxidative stress, and inflammation. Considering the antioxidant properties of pomegranate peel extract, this study was conducted to determine the effects of pomegranate peel consumption on some metabolic features in patients with NAFLD. Our hypothesis is that pomegranate peel can improve the grade of fatty liver, liver enzymes, lipid profile, serum high-sensitivity C-reactive protein (hs-CRP), and anthropometric indices. The aim of this study was to investigate the efficacy of pomegranate peel extract in NAFLD patients. This double-blind randomized clinical trial was conducted on 46 patients with NAFLD. Patients were randomly assigned to intervention group (n = 23) and placebo group (n = 23). Patients in the pomegranate peel group consumed two capsules, each containing 500 mg pomegranate peel extract daily as a part of low-calorie diet (i.e., 500-deficit calorie diet) for 10 weeks. While patients in the control group followed the low calorie diet and two capsules containing 500 mg maltodextrin. At the beginning and end of the study, demographic information, anthropometric indices, food intake, physical activity level, grade of fatty liver, liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) were measured. Food intake was measured by 24-h food recall questionnaires and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Analysis of food recall questionnaire was done using Nutritionist IV program. Statistical analysis was performed using SPSS software (version 22), and a p value < 0.05 was defined as statistically significant. Of 46 patients, 42 of them completed the trial. At the end of the trial, pomegranate peel group had significantly higher reduction in TG (triglycerides), ALT(alanine aminotransferase), AST(aspartate transferase), hs-CRP and also had higher significant increase in HDL-C(high-density lipoprotein cholesterol) compared to the control group (p = 0/02, p = 0/02, p = 0/01, p = 0/01, and p = 0/04, respectively). However, changes in LDL-C, TC, ALP, GGT, and fatty liver grade were not significantly different between the two groups at the end of the study. The current study indicates that pomegranate peel extract has a favorable effect on liver enzymes, lipid profile, and serum high-sensitivity C-reactive protein (hs-CRP) in patients with NAFLD. To support these results, trials examining various dosages over longer time periods are necessary.