Puerarin Induces Macrophage M2 Polarization to Exert Antinonalcoholic Steatohepatitis Pharmacological Activity via the Activation of Autophagy.

To determine the protective mechanism of puerarin against nonalcoholic steatohepatitis (NASH), the pharmacodynamic effects of puerarin on NASH were evaluated by using zebrafish, cells, and mice. Western blotting, flow cytometry, immunofluorescence, and qRT-PCR were used to detect the effects of puerarin on RAW264.7 autophagy and polarization. Key target interactions between autophagy and polarization were detected using immunoprecipitation. Puerarin regulated the M1/M2 ratio of RAW 264.7 cells induced by LPS + INF-γ. Transcriptomics revealed that PAI-1 is a key target of puerarin in regulating macrophage polarization. PAI-1 knockout reduced the number of M1-type macrophages and increased the number of M2-type macrophages. Puerarin regulated PAI-1 and was associated with macrophage autophagy. It increased p-ULK1 expression in macrophages and activated autophagic flux, reducing the level of PAI-1 expression. Stat3/Hif-1α and PI3K/AKT signaling pathways regulated the number of macrophage polarization phenotypes, reducing liver lipid droplet formation, alleviating liver structural abnormalities, decreasing the number of cytoplasmic vacuoles, and decreasing the area of blue collagen in NASH mice. Puerarin is a promising dietary component for NASH alleviation.

Anti-Colorectal Cancer Activity of Solasonin from Solanum nigrum L. via Histone Deacetylases-Mediated p53 Acetylation Pathway.

(1) Background: Solanum nigrum L. is a plant of the genus Solanum in the family Solanaceae and is commonly used to treat tumors. Solasonin (SS) is a steroidal alkaloid extracted from Solanum nigrum L. that has anti-colorectal cancer (CRC) activity. (2) Methods: Column chromatography, semi-preparative HPLC and cellular activity screening were used to isolate potential anti-CRC active compounds in Solanum nigrum L., and structure identification using 1H-NMR and 13C-NMR techniques. Expression levels of HDAC in CRC were mined in the UALCAN database. The in vitro effects of SS on SW620 cell line and its mechanism were examined via Western blot, EdU staining, flow cytometry and immunofluorescence. CRC xenograft model and IHC staining were mainly used to evaluate the role of SS in vivo. (3) Results: The results showed that SS was the most potent anti-CRC component in Solanum nigrum L., which induced apoptosis and cell cycle arrest in the SW620 cell line. HDAC was highly expressed in CRC. The treatment of SW620 cell line with SS resulted in a significant downregulation of HDAC, an increase in the level of P53 acetylation and a subsequent increase in the level of P21. The in vivo validation results showed that SS could effectively inhibit CRC growth, which was associated with the downregulation of HDAC. (4) Conclusions: SS treatment for CRC mainly works through the induction of apoptosis and cycle arrest, and its mechanism of action is mainly related to HDAC-induced P53 acetylation, and the HDAC/P53 signaling pathway may be a potential pathway for the treatment of CRC.

American Ginseng for the Treatment of Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a prevalent degenerative condition that is increasingly affecting populations globally. American ginseng (AG) has anti-AD bioactivity, and ginsenosides, as the main active components of AG, have shown strong anti-AD effects in both in vitro and in vivo studies. It has been reported that ginsenosides can inhibit amyloid ß-protein (Aß) production and deposition, tau phosphorylation, apoptosis and cytotoxicity, as well as possess anti-oxidant and anti-inflammatory properties, thus suppressing the progression of AD. In this review, we aim to provide a comprehensive overview of the pathogenesis of AD, the potential anti-AD effects of ginsenosides found in AG, and the underlying molecular mechanisms associated with these effects. Additionally, we will discuss the potential use of AG in the treatment of AD, and how ginsenosides in AG may exert more potent anti-AD effects in vivo may be a direction for further research.

Preventive and therapeutic effects of natural products and herbal extracts on nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is a common condition that is prevalent in patients who consume little or no alcohol, and is characterized by excessive fat accumulation in the liver. The disease is becoming increasingly common with the rapid economic development of countries. Long-term accumulation of excess fat can lead to NAFLD, which represents a global health problem with no effective therapeutic approach. NAFLD is a complex, multifaceted pathological process that has been the subject of extensive research over the past few decades. Herbal medicines have gained attention as potential therapeutic agents to prevent and treat NAFLD due to their high efficacy and low risk of side effects. Our overview is based on a PubMed and Web of Science database search as of Dec 22 with the keywords: NAFLD/NASH Natural products and NAFLD/NASH Herbal extract. In this review, we evaluate the use of herbal medicines in the treatment of NAFLD. These natural resources have the potential to inform innovative drug research and the development of treatments for NAFLD in the future.

Renal function protection and the mechanism of ginsenosides: Current progress and future perspectives.

Nephropathy is a general term for kidney diseases, which refers to changes in the structure and function of the kidney caused by various factors, resulting in pathological damage to the kidney, abnormal blood or urine components, and other diseases. The main manifestations of kidney disease include hematuria, albuminuria, edema, hypertension, anemia, lower back pain, oliguria, and other symptoms. Early detection, diagnosis, and active treatment are required to prevent chronic renal failure. The concept of nephropathy encompasses a wide range of conditions, including acute renal injury, chronic kidney disease, nephritis, renal fibrosis, and diabetic nephropathy. Some of these kidney-related diseases are interrelated and may lead to serious complications without effective control. In serious cases, it can also develop into chronic renal dysfunction and eventually end-stage renal disease. As a result, it seriously affects the quality of life of patients and places a great economic burden on society and families. Ginsenoside is one of the main active components of ginseng, with anti-inflammatory, anti-tumor, antioxidant, and other pharmacological activities. A variety of monomers in ginsenosides can play protective roles in multiple organs. According to the difference of core structure, ginsenosides can be divided into protopanaxadiol-type (including Rb1, Rb3, Rg3, Rh2, Rd and CK, etc.), and protopanaxatriol (protopanaxatriol)- type (including Rg1, Rg2 and Rh1, etc.), and other types (including Rg5, Rh4, Rh3, Rk1, and Rk3, etc.). All of these ginsenosides showed significant renal function protection, which can reduce renal damage in renal injury, nephritis, renal fibrosis, and diabetic nephropathy models. This review summarizes reports on renal function protection and the mechanisms of action of these ginsenosides in various renal injury models.

Anti-cancer effect and potential microRNAs targets of ginsenosides against breast cancer.

Breast cancer (BC) is one of the most common malignant tumor, the incidence of which has increased worldwide in recent years. Ginsenosides are the main active components of Panax ginseng C. A. Mey., in vitro and in vivo studies have confirmed that ginsenosides have significant anti-cancer activity, including BC. It is reported that ginsenosides can induce BC cells apoptosis, inhibit BC cells proliferation, migration, invasion, as well as autophagy and angiogenesis, thereby suppress the procession of BC. In this review, the therapeutic effects and the molecular mechanisms of ginsenosides on BC will be summarized. And the combination strategy of ginsenosides with other drugs on BC will also be discussed. In addition, epigenetic changes, especially microRNAs (miRNAs) targeted by ginsenosides in the treatment of BC are clarified.

Salvia miltiorrhiza in cancer: Potential role in regulating MicroRNAs and epigenetic enzymes.

MicroRNAs are small non-coding RNAs that play important roles in gene regulation by influencing the translation and longevity of various target mRNAs and the expression of various target genes as well as by modifying histones and DNA methylation of promoter sites. Consequently, when dysregulated, microRNAs are involved in the development and progression of a variety of diseases, including cancer, by affecting cell growth, proliferation, differentiation, migration, and apoptosis. Preparations from the dried root and rhizome of Salvia miltiorrhiza Bge (Lamiaceae), also known as red sage or danshen, are widely used for treating cardiovascular diseases. Accumulating data suggest that certain bioactive constituents of this plant, particularly tanshinones, have broad antitumor effects by interfering with microRNAs and epigenetic enzymes. This paper reviews the evidence for the antineoplastic activities of S. miltiorrhiza constituents by causing or promoting cell cycle arrest, apoptosis, autophagy, epithelial-mesenchymal transition, angiogenesis, and epigenetic changes to provide an outlook on their future roles in the treatment of cancer, both alone and in combination with other modalities.