Phytotherapy Research最新文献

Knee osteoarthritis (OA) has recently been ranked as the 11th highest contributor to global disability. More than 40% of patients use complementary and alternative medicine including supplements containing phytoextracts with anti-inflammatory properties as those from the Boswellia genus. The aim of this meta-analysis was to evaluate the efficacy of phytoextracts from the oleogum resin of the Boswellia genus as supplementation for patients affected by knee OA. Four electronic databases were used for the research and PRISMA statements were followed throughout the study. The following inclusion criteria were used: (a) the subjects of the study were humans with a diagnosis of knee OA reported by medical staff; (b) randomization and the presence of control (placebo, negative or positive control), and (c) outcomes reported with WOMAC and/or visual analog scale (VAS) score. Publication bias was assessed with a funnel plot and through the Egger test. The Jadad scale was used in order to assess the quality of the studies included. The statistical heterogeneity was assessed using I² statistics. Results of meta-analysis and subgroup analysis were reported using a forest plot. A total of 13 studies involving 850 (WOMAC) and 1185 (VAS) patients met the inclusion criteria. The meta-analysis did not detect a significant effect of the use of Boswellia extracts between the control and the treatment groups due to the high heterogeneity of the studies (p = 0.0865 for WOMAC) and (p = 0.3966 VAS). However, the subsequent subgroup analysis demonstrated the significant beneficial effect of Boswellia extracts in the treatment of knee OA with respect to a placebo (lower WOMAC score in the treatment groups). This was also confirmed in the meta-regression applied to the WOMAC scores. This is an important finding as people exposed to NSAID-related adverse effects could benefit from the use of Boswellia extracts. However, further high-quality studies are needed to establish the clinical efficacy of extracts from the genus Boswellia.

Liver disease represents a significant global public health concern. Silybin, derived from Silybum marianum, has been demonstrated to exhibit a range of beneficial properties, including anti-inflammatory, antioxidative, antifibrotic, antiviral, and cytoprotective effects. These attributes render it a promising candidate for the treatment of liver fibrosis, cirrhosis, liver cancer, viral hepatitis, non-alcoholic fatty liver disease, and other liver conditions. Nevertheless, its low solubility and low bioavailability have emerged as significant limitations in its clinical application. To address these limitations, researchers have developed a number of silybin formulations. This study presents a comprehensive review of the results of research on silybin for the treatment of liver diseases in recent decades, with a particular focus on novel formulations based on the pathogenesis of the disease. These include approaches targeting the liver via the CD44 receptor, folic acid, vitamin A, and others. Furthermore, the study presents the findings of studies that have employed nanotechnology to enhance the low bioavailability and low solubility of silybin. This includes the use of nanoparticles, liposomes, and nanosuspensions. This study reviews the application of silybin preparations in the treatment of global liver diseases. However, further high-quality and more complete experimental studies are still required to gain a more comprehensive understanding of the efficacy and safety of these preparations. Finally, the study considers the issues that arise during the research of silybin formulations.

Despite remarkable breakthroughs in pharmacotherapy, many potential therapies for aging remain unexplored. Punicalin (PUN), an ellagitannin component, exerts anti-inflammatory, antioxidant, and anti-apoptotic effects. This study investigated the beneficial effects of PUN against age-related brain damage in mice and explored the underlying mechanisms. We validated the protective effects of PUN against D-galactose (D-gal)-induced neuroinflammation and subsequent neuronal damage in BV2 microglia and N2a cells, respectively, in vitro. In vivo experiments were conducted on mice that were administered an 8-week regimen of intraperitoneal injections of D-gal at a dosage of 150 mg/kg/day, concurrently with oral gavage of PUN at the same dose. PUN inhibited the production of D-gal-induced inflammatory cytokines (iNOS, COX2, TNF-α, IL-6, IL-2, and IL-1β) in BV2 cells and conferred protection to N2a cells against synaptic damage mediated by BV2 microglia-induced neuroinflammation. The in vivo findings revealed that PUN considerably improved memory and learning deficits, reduced MDA levels, enhanced GSH-Px, CAT, and SOD activities, and modulated the expression of inflammatory proteins such as iNOS, COX-2, IL-1β, IL-2, IL-6, and TNF-α. Furthermore, PUN inhibited the secretion of SASP factors (ICAM-1, PAI-1, MMP-3, and MMP-9), decreased microglial activation, and reduced astrocytosis. Additionally, PUN suppressed the expression of cGAS, p-STING, p-TBK1, p-p65, and p-IRF3 in aging mouse brains and cultured BV2 microglia. In conclusion, PUN improved cognitive dysfunction in aging mice through antioxidant and anti-inflammatory mechanisms via inhibition of the cGAS-STING pathway, suggesting that it can be a promising therapeutic agent for brain aging and aging-related diseases.

The prevalence of diabetes is escalating alarmingly, placing a significant economic burden on the global healthcare system. The use of chemical substances extracted from plants has been demonstrated to be an effective method for the treatment and control of insulin resistance and Type 2 diabetes mellitus (T2DM). New research indicates that natural phytochemicals present in fruits and vegetables are expected to become drugs for the treatment of diabetes and the prevention of related complications. Quercetin, a widely distributed flavonoid, is well-known for its antioxidant, anti-inflammatory, anticancer, and antidiabetic properties. This article provides a comprehensive account of the mechanism of action of quercetin on diabetes and obesity complications in vivo and in vitro. It elucidates the impact of quercetin on various cells. These include hepatocytes, renal cells, skeletal muscle cells, and adipocytes. Furthermore, this article discusses the mechanism of quercetin on organ damage in diabetic mice induced by STZ, alloxan, diet, and spontaneous Type 2 diabetic mice caused by genetic defects. Additionally, it addresses the pharmacokinetics of quercetin and its potential for synergistic effects with existing diabetic drugs.

High-altitude pulmonary edema (HAPE) is a life-threatening disease, and autophagy deficiency is implicated in the pathogenesis of HAPE. Eleutheroside B (EB), which is the main bioactive component of Acanthopanax senticosus, exhibits various pharmacological activities. Our previous research demonstrated that autophagic structures were widely found in the ultrastructure of lung tissue in HAPE rats. However, whether EB regulates autophagy deficiency in HAPE remains unknown. This study aimed to investigate the protective effects of EB on hypobaric hypoxia-induced HAPE and explore the underlying molecular mechanism of regulating autophagy. The rat model of high-altitude pulmonary edema was replicated using a hypobaric hypoxic chamber. Rats were pretreated with EB or in combination with chloroquine or compound C. The pulmonary edema was assessed by the lung wet/dry ratio, total protein concentration in bronchoalveolar lavage fluid, and histological analysis. Inflammation and oxidative stress were measured using commercial biochemical kits. Autophagy and autophagic flux were evaluated by western blotting, transmission electron microscopy, and adeno-associated virus-mRFP-GFP-labeled tandem fluorescence LC3. The AMPK/mTOR signaling pathway was detected by western blotting. EB alleviated hypobaric hypoxia-induced pulmonary edema, hypoxemia, acid-base imbalance in the blood, inflammation, and oxidative stress in a dose-dependent manner. EB restored impaired autophagic flux by activating the AMPK/mTOR signaling pathway. However, chloroquine or compound C abolished eleutheroside B-mediated autophagy flux restoration. EB has the potential to restore impaired autophagic flux in the lung of hypobaric hypoxia-induced HAPE rats, which could be attributed to the activation of AMPK/mTOR signaling pathway.

Oxidative stress plays an important role in the occurrence of neurodegenerative diseases. Previous studies indicate a strong connection between oxidative stress, inappropriate activation of the p38 MAPK signaling pathway, and the pathogenesis of neurodegenerative diseases. Although antioxidant therapy is a valid strategy to alleviate these problems, the most important limitation of this approach is the ineffectiveness of drug administration due to the limited permeability of the BBB. Therefore, BBB-penetrating p38 MAPK modulators with proper antioxidant capacity could be useful in preventing/reducing the complications of neurodegenerative disorders. The current manuscript aims to review the therapeutic capabilities of some recently reviewed naturally occurring p38 MAPK inhibitors in the management of neurodegenerative problems such as Alzheimer's disease. In data collection, we tried to use more recent studies published in high-quality journals indexed in databases Scopus, Web of Science, PubMed, and so on, but no specific time frame was considered due to the nature of the study. Our evaluations indicate that natural compounds tanshinones, protoberberines, pinocembrin, osthole, rhynchophylline, oxymatrine, schisandrin, piperine, paeonol, ferulic acid, 6-gingerol, obovatol, and trolox have significant potential for use as supplements/adjuvants in the reduction of neurodegenerative-related problems. Our findings emphasize the usefulness of BBB-penetrating phytochemicals with p38 MAPK modulatory activity as potential therapeutic options against neurodegenerative disorders. Of course, the proper use of these compounds depends on considering their toxicity/safety profile and pharmacokinetic characteristics as well as the clinical conditions of users.

Cancer incidence has increased globally and has become the leading cause of death in the majority of countries. Many cancers have altered energy metabolism pathways, such as increased glucose uptake and glycolysis, as well as decreased oxidative phosphorylation. This is known as the Warburg effect, where cancer cells become more reliant on glucose to generate energy and produce lactate as an end product, even when oxygen is present. These are attributed to the overexpression of key glycolytic enzymes, glucose transporters, and related signaling pathways that occur in cancer cells. Therefore, overcoming metabolic alterations in cancer cells has recently become a target for therapeutic approaches. Natural products have played a key role in drug discovery, especially for cancer and infectious diseases. In this review, we are going to focus on terpenoids, which are gradually gaining popularity among drug researchers due to their reported anti-cancer effects via cell cycle arrest, induction of apoptosis, reduction of proliferation, and metastasis. This review summarizes the potential of 13 terpenoid compounds as anti-glycolytic inhibitors in different cancer models, primarily by inhibiting the glucose uptake and the generation of lactate, as well as by downregulating enzymes associated to glycolysis. As a conclusion, disruption of cancer cell glycolysis may be responsible for the anti-cancer activity of terpenoids.