The American Journal of Chinese Medicine

Recent research has extensively explored the intricate mechanisms that underlie the effectiveness of acupuncture, highlighting the importance of stimulating acupoints, the role of acupuncture techniques in managing diseases, and the interaction between meridian pathways and molecular processes. Studies have underscored the crucial role of acupuncture in activating neurons, modulating the immune system, and influencing vascular activity, all of which contribute significantly to its therapeutic benefits across a wide range of symptoms and conditions. Utilization of imaging modalities enables the identification of changes in cerebral blood flow, brain function, and regional glucose metabolism following acupuncture sessions. The interstitial fluid circulation network within meridians adheres to specific laws that facilitate the transportation of materials. Acupuncture initiates the release of neurotransmitters, neuropeptides, and immune factors, impacting pain perception, inflammation, and physiological functions. It influences the complex neuro–endocrine–immune network by activating pathways involving the nervous system, the hypothalamic-pituitary-adrenal axis, and immune responses. Moreover, acupuncture induces molecular modifications such as phosphorylation, methylation, and histone modification, leading to key molecular changes that ultimately result in anti-inflammatory effects and the regulation of immune responses.

There have been numerous studies investigating the impact of acupuncture and/or moxibustion on the gut microbiota, but the results have been inconclusive. Therefore, we conducted a systematic review and meta-analysis that included both preclinical and clinical studies to assess the current evidence regarding the effects of acupuncture on gut microbiota changes. We collected relevant studies from EMBASE and PubMed, collected outcomes including diversity and relative abundance measures of the gut microbiome, and the summarized effect estimates were calculated using the ratio of means (ROM) with 95% confidence intervals. Our analysis identified three clinical studies and 20 preclinical studies, encompassing various diseases and models, including colitis and obesity. The pooled results indicated no significant difference in alpha diversity changes between treatment groups and controls, except for the Simpson index measure, which was significantly higher in the treatment groups. Additionally, the pooled results showed an increase in the Firmicutes and a decrease in the Bacteroidetes in the treatment groups, along with increases in the Lactobacillus and Ruminococcus genera. These findings suggest acupuncture treatment can target the modification of specific phyla and genera of gut microbiota. However, it is important to note that the effects of acupuncture on the gut microbiome are heterogeneous across studies, particularly in different disease models.

Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.

Osteoporosis is the most common bone metabolic disease, and it is becoming increasingly common as the global population ages. Osteoporosis and its complications, such as fractures and pain, negatively affect patient quality of life and easily lead to disability, placing enormous burdens on society. Although several anti-osteoporosis drugs are currently available, many adverse reactions have been observed during the long-term application of these drugs. Therefore, safer and more useful medications are urgently needed to replace those currently available. Chinese herbal medicine has been extensively used to treat osteoporosis, and the current literature confirms that such medicines have anti-osteoporosis effects, are safe, and have minimal side effects. Thus, Chinese herbal medicines are natural alternatives to pharmaceutical approaches to treating osteoporosis, and these medicines must be further developed and utilized. In this article, we review the mechanisms underlying the anti-osteoporosis effects of single herbal extracts and traditional Chinese medicine (TCM) formulas that have been elucidated since 2013, providing key evidence and support for future research on the anti-osteoporosis effects of Chinese herbal medicines. In addition, due to the complexity of the ingredients in Chinese herbal medicine, more thorough investigations are needed to determine the specific ingredients that are effective in osteoporosis treatment. Therefore, identifying the effective ingredients of Chinese herbal medicines will be a necessary focus in laboratory research and clinical application.

Taxus, a rare and protected genus predominantly distributed across the Northern Hemisphere’s temperate regions, has garnered global attention due to its significant potential in medical research and pharmaceutical development, bolstered by advancements in cultivation techniques and medical technology. This review primarily focuses on the chemical constituents and pharmacological activities of Taxus, underscoring the progress and potential of these components in clinical applications. Recent studies have revealed that Taxus contains not only taxane active components but also flavonoids and polysaccharides with distinct activities. These compounds from Taxus exhibit potent antitumor, anti-inflammatory, immunomodulatory, antibacterial, and antidiabetic properties with evident mechanisms of action. Notably, the representative compound, paclitaxel, has demonstrated significant efficacy in treating various cancers, such as ovarian, breast, and lung cancer. This paper also reviews the basic situation of Taxus drug formulations, with extracts primarily administered orally and monomeric taxanes typically via injection, reflecting a mature development stage with ongoing research into oral formulations. Finally, this review summarizes the pharmacokinetic characteristics of crucial compounds in Taxus, including their absorption, distribution, metabolism, and excretion patterns in the human body. These pharmacokinetic profiles provide crucial guidance for evaluating the overall dosing regimen of Taxus and its components. The paper concludes with a forward-looking analysis of the potential applications of these compounds in disease treatment, envisioning their role in the future of medical and pharmaceutical advancements.

Salvianolic acid B (SalB), among the most abundant bioactive polyphenolic compounds found in Salvia miltiorrhiza Bge., exerts therapeutic and protective effects against various diseases. Although some summaries of the activities of SalB exist, there is lack of a scientometric and in-depth review regarding disease therapy. In this review, scientometrics was employed to analyze the number of articles, publication trends, countries, institutions, keywords, and highly cited papers pertaining to SalB research. The scientometric findings showed that SalB exerts excellent protective effects on the heart, lungs, liver, bones, and brain, along with significant therapeutic effects against atherosclerosis (AS), Alzheimer’s disease (AD), liver fibrosis, diabetes, heart/brain ischemia, and osteoporosis, by regulating signaling pathways and acting on specific molecular targets. Moreover, this review delves into in-depth insights and perspectives, such as the utilization of SalB in combination with other drugs, the validation of molecular mechanisms and targets, and the research and development of novel drug carriers and dosage forms. In conclusion, this review aimed to offer a comprehensive scientometric analysis and in-depth appraisal of SalB research, encompassing both present achievements and future prospects, thereby providing a valuable resource for the clinical application and therapeutic exploitation of SalB.

Osthole, a coumarin compound mainly derived from Cnidium monnieri (L.), has attracted much interest from the scientific community owing to its multiple therapeutic properties. However, its pharmacological mechanism, pharmacokinetics, and toxicological effects are far from clear. Furthermore, the potential drug delivery platforms of osthole remain to be comprehensively delineated. The present review aimed to systematically summarize the most up-to-date information related to pharmacology, pharmacokinetics, and safety issues related to osthole, and discuss the investigations of novel drug delivery platforms. The information herein discussed was retrieved from authoritative databases, including PubMed, Web of Science, Google Scholar, Chinese National Knowledge Infrastructure (CNKI) and so on, reviewing information published up until February of 2024. New evidence shows that osthole induces a sequence of therapeutic actions and has a moderate absorption rate and rapid metabolic characteristics. In addition, this phytoconstituent possesses potential hepatotoxicity, and caution should be exercised against the risk of the drug combination. Furthermore, given its needy solubility in aqueous medium and non-organizational targeting, novel drug delivery methods have been designed to overcome these shortcomings. Given the properties of osthole, its therapeutic benefits ought to be elucidated in a greater array of comprehensive research studies, and the molecular mechanisms underlying these benefits should be explored.

Aging is an irresistible natural law of the progressive decline of body molecules, organs, and overall function with the passage of time, resulting in eventual death. World Health Organization data show that aging is correlated with a wide range of common chronic diseases in the elderly, and is an essential driver of many diseases. Panax Ginseng C.A Meyer is an ancient herbal medicine, which has an effect of “long service, light weight, and longevity” recorded in the ancient Chinese medicine book “Compendium of Materia Medica.” Ginsenoside Rg2, the main active ingredient of ginseng, also exerts a marked effect on the treatment of liver injury. However, it remains unclear whether Rg2 has the potential to ameliorate aging-induced liver injury. Hence, exploring the hepatoprotective properties of Rg2 and its possible molecular mechanism by Senescence Accelerate Mouse Prone 8 (SAMP8) and gut microbiota. Our study demonstrated that Rg2 can inhibit pyroptosis and apoptosis through caspase 8, and regulate the gut-liver axis to alleviate liver inflammation by changing the composition of gut microbiota, thus improving aging-induced liver injury. These findings provide theoretical support for the pharmacological effects of ginsenosides in delaying aging-induced liver injury.

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease — most prominently renal anemia and renal fibrosis — have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-κB inhibitors (PDTC), validated CAT’s ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-κB p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-κB, and then inhibited the expression of IL-6, p-STAS3, TGF-β1 protein. Therefore, CAT can regulate Nrf2/NF-κB signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys.

Recent research has indicated that formononetin demonstrates a potent anti-inflammatory effect in various diseases. However, its impact on sterile inflammation kidney injury, specifically acute kidney injury (AKI), remains unclear. In this study, we utilized an ischemia/reperfusion-induced AKI (IRI-AKI) mouse model and bone marrow-derived macrophages (BMDMs) to investigate the effects of formononetin on sterile inflammation of AKI and to explore the underlying mechanism. The administration of formononetin significantly preserved kidney function from injury, as evidenced by lower serum creatinine and blood urea nitrogen levels compared to IRI-AKI mice without treatment. This was further confirmed by less pathological changes in renal tubules and low expression of tubular injury markers such as KIM-1 and NGAL in the formononetin-treated IRI-AKI group. Furthermore, formononetin effectively suppressed the expression of pro-inflammatory cytokines (MCP-1, TNF-α, and IL-1β) and macrophage infiltration into the kidneys of AKI mice. In vitro studies showed that formononetin led to less macrophage polarization towards a pro-inflammatory phenotype in BMDMs stimulated by LPS and IFN-$\gamma$. The mechanism involved the KLF6 and p-STAT3 pathway, as overexpression of KLF6 restored pro-inflammatory cytokine levels and pro-inflammatory polarization. Our findings demonstrate that formononetin can significantly improve renal function and reduce inflammation in IRI-AKI, which may be attributed to the inhibition of KLF6/STAT3-mediated macrophage pro-inflammatory polarization. This discovery presents a new promising therapeutic option for the treatment of IRI-AKI.

Acute kidney injury (AKI) is a major public health problem worldwide that still lacks effective treatments. Recent studies have suggested that ferroptosis is a key mediator of AKI due to its activation of lipid peroxidation. Therefore, we hypothesized that antiferroptosis agents might be a novel potential therapeutic strategy for AKI. Herein, we demonstrated that liquiritigenin (LG), an active ingredient of liquorice, improves renal function by inhibiting vitamin K epoxide reductase complex subunit 1 (VKORC1)-mediated ferroptosis, both in vivo and in vitro. In a folic acid-induced murine AKI model, after a single pre-treatment intravenous injection, LG markedly alleviated the loss of renal function through suppressing ferroptosis induced by iron accumulation. LG prevented mitochondrial morphological changes and upregulated glutathione and glutathione peroxidase 4 levels, while downregulating malonaldehyde and divalent iron levels. An in vitro RNA-sequence analysis suggested that the protective role of LG may involve upregulation of VKORC1. Moreover, knockdown of VKORC1 diminished the renal protective and antiferroptosis roles of LG. Collectively, our findings demonstrated that LG protected against AKI by inhibiting VKORC1-mediated ferroptosis. This suggests that inhibiting ferroptosis might be a novel therapeutic approach in the future.

Astragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed $Ap{c}^{\text{Min}∕+}$ mice. $Ap{c}^{\text{Min}∕+}$ mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1β, IL-6, and TNF-α), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/β-catenin pathway proteins (Wnt3a, β-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed $Ap{c}^{\text{Min}∕+}$ mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed $Ap{c}^{\text{Min}∕+}$ mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/β-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV’s antitumor effects.