Chronic obstructive pulmonary disease (COPD) is a prevalent, preventable, and treatable chronic airway disease associated with high morbidity, mortality, and global burden. In this review, we searched PubMed, Web of Science, and major Chinese academic databases for clinical and mechanistic studies of traditional Chinese medicine (TCM) interventions for COPD, emphasizing evidence relevant to the stable phase, acute exacerbation phase, and first 8 weeks after an exacerbation, termed the acute exacerbation of COPD (AECOPD) risk window phase (risk window). Evidence from randomized trials and evidence syntheses indicates that adjunctive herbal formulae, Chinese patent medicines, acupuncture, moxibustion, acupoint-based interventions, and traditional Chinese exercise therapy may improve symptoms, the 6-minute walking distance (6MWD), pulmonary function indices, quality of life, and selected exacerbation-related outcomes. Multicenter trials have also reported benefits of syndrome-based sequential treatment during acute exacerbation and the subsequent risk window. Mechanistic studies suggest coordinated regulation of inflammatory and oxidative stress pathways, immune homeostasis, epithelial barrier integrity, mucus hypersecretion, apoptosis, and airway remodeling. However, confidence in these findings is limited by heterogeneous syndrome definitions and intervention protocols, small samples, incomplete blinding and allocation reporting, and insufficient long-term follow-up. Future research should prioritize standardized diagnostic criteria and outcomes, rigorously designed multicenter trials, and translational studies that link in vivo active substances and molecular targets to clinically meaningful outcomes.
Natural products and bioactive constituents derived from traditional Chinese medicine (TCM) are major sources of innovation in modern drug discovery and formulation because of their remarkable structural diversity and multidimensional pharmacological activities. However, their clinical translation is frequently hindered by poor solubility, limited stability, low systemic exposure, inefficient tissue delivery, and narrow therapeutic windows. In recent years, drug delivery technologies have advanced the field beyond conventional solubilization, stabilization, and encapsulation toward more integrated strategies that enable targeted delivery, barrier penetration, microenvironment-responsive release, and combination therapy. More importantly, certain natural products are no longer regarded solely as therapeutic cargoes but are increasingly repurposed as functional excipients that enhance structural assembly, delivery efficiency, targeting, and pharmacological synergy. This shift is driving a transition from formulation optimization centered on single active ingredients to integrated drug–excipient design. It also enables contemporary delivery science to reconnect with the holistic philosophy of TCM and the compatibility principles embodied in the monarch, minister, assistant, and guide framework. In this review, we examine the dual roles of natural products in drug delivery systems. We first summarize the developability barriers, delivery mechanisms, and representative optimization strategies associated with their application as therapeutic agents. We then highlight their emerging functions as excipients, focusing on key functional roles, construction paradigms, and recent advances in multifunctional delivery platforms integrating lipid nanoparticles, proteins, antibodies, nucleic acids, and living therapeutics. We further outline representative preclinical applications in cancer, neurodegenerative, metabolic, inflammatory, and immune-related diseases. Collectively, research on natural product–based delivery systems is evolving from single-formulation optimization toward integrated design guided by disease context, material functionality, and the holistic principles of TCM, thereby providing new conceptual and technological foundations for formulation innovation and clinical translation.
Aberrant eating behavior constitutes a critical bottleneck in both the development of obesity and the maintenance of weight loss. This review focused on the role of acupuncture in regulating eating behavior for weight loss. Most studies have focused on the regulation of body weight or body mass index but have overlooked the role of eating behaviors. As a non-pharmacological intervention for weight loss, acupuncture offers multitarget advantages that call for an in-depth analysis from the perspective of eating. This review focused on the novel perspective that the core mechanism of acupuncture for weight loss relies on the synergy of multiple pathways involving the central nervous system, gut microbiota, and vagus nerve. The central mechanism of acupuncture for weight loss may lie in restoring the imbalance between the neuropeptide Y/agouti-related protein and pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus, as well as improving the function of the prefrontal–limbic system, thereby inhibiting emotional eating. At the peripheral level, acupuncture may maintain leptin–ghrelin homeostasis, inhibit tumor necrosis factoralpha or interleukin-6–mediated inflammation, and affect intestinal barrier repair and reconstruction of eating signaling pathways. To address the limitations of current studies, such as the lack of functional magnetic resonance imaging or positron emission tomography neuroimaging evidence, small sample sizes, short follow-up durations, and non-individualized protocols, this review proposes integrated research strategies, including incorporating eating behavior assessment scales, utilizing multi-omics to identify core targets, and conducting multicenter, large-sample, randomized controlled trials. These solutions aim to advance acupuncture from an empirical therapy to precise management, thereby providing novel strategies for obesity prevention and treatment that integrate mechanistic innovations with clinical translational value.
Insomnia is a common comorbidity and a recognized risk factor among individuals with substance use disorder (SUD). It is imperative to consider nonpharmacological adjunct therapies for bidirectional effects when treating insomnia in individuals with SUD. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of acupuncture for treating insomnia in individuals with SUD.
Electronic databases were searched from inception to December 2024 to identify relevant randomized controlled trials (RCTs) comparing needle acupuncture with sham acupuncture, conventional care, non-acupuncture active treatment, or waitlist controls in patients with insomnia and SUD. The primary outcome was sleep quality, which was measured using the Pittsburgh Sleep Quality Index (PSQI) (lower scores indicate better sleep quality). Pooled effects were estimated using random-effects models. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Trial sequential analysis (TSA) was used to assess the risk of false-positive and false-negative results.
Eighteen RCTs with 1,750 participants met the inclusion criteria. All the RCTs were conducted in China. Sixteen RCTs had a moderate-to-high risk of bias. The pooled results showed that manual acupuncture (MA) yielded a better total PSQI score than sham acupuncture (mean difference [MD], -2.15 [95% confidence interval [CI], -2.93 to -1.38], P < 0.00001; minimal clinically important difference (MCID): -1.25), with low-certainty evidence. The TSA results suggested that the required information volume had been reached, indicating that additional trials may not be necessary in terms of sample size. Subgroup analyses revealed that acupuncture interventions had a greater effect among individuals with opioid use disorder (OUD) (MD, -1.93 [95% CI, -2.61 to -1.25], P < 0.00001) than on those with alcohol use disorder (MD, -1.49 [95% CI, -2.12 to -0.87], P < 0.00001) or new drug use disorder (MD, -3.94 [95% CI, -7.99 to 0.12], P = 0.06). However, the evidence regarding the efficacy of other forms of acupuncture and the comparative effectiveness between various forms of acupuncture was limited.
A review of 18 RCTs provides low-certainty evidence that MA may be more effective than sham acupuncture for improving sleep quality in individuals with SUD, with the effect potentially stronger among those with OUD. Given that most of the included studies exhibited a moderate-to-high risk of bias, the strength of the conclusions should be interpreted with caution. Therefore, additional research on the use of acupuncture to alleviate insomnia and reduce SUD withdrawal symptoms is warranted.
Daphnegiravone D (DGD), a prenylated flavonoid from Daphne giraldii Nitsche, a plant whose roots and stem are used in Chinese medicine, exerts an inhibitory effect on liver cancer cells. The protein kinase ataxia telangiectasia-mutated and Rad3-related (ATR) is an important component of the DNA damage response, and its inhibition enhances the sensitivity of some cancer cells to DNA-damaging drugs. Oxaliplatin (OXA) is a third-generation, platinum-based anticancer drug that exerts its inhibitory effects on liver cancer cells by inhibiting DNA synthesis. Owing to the fact that most patients develop drug resistance, finding novel treatments for liver cancer is urgent. In a previous study, DGD was shown to exert anti-tumor effects as a potential ATR kinase inhibitor. This study investigated the mechanism of action of DGD and its combination with OXA in liver cancer.
HepG2 and Hep3B cells were used to evaluate the inhibitory effects of DGD on liver cancer. Cellular thermal shift assay, co-immunoprecipitation, and western blotting were used to confirm the impact of DGD on DNA damage. The methyl thiazolyl tetrazolium (MTT) assay was performed, and the resulting data were used to calculate drug synergy scores. Acridine orange/ethidium bromide staining, Annexin V/propidium iodide staining, reactive oxygen species–related staining, and western blotting were performed to assess the efficacy of the combination of DGD and OXA. An in vivo tumor xenograft model in nude mice was used to investigate the efficacy of this combination. Hematoxylin–eosin staining and immunohistochemistry were performed to observe the condition of tissues in vivo.
DGD inhibited liver cancer cells by affecting the formation of the ATR-ATRIP complex and downregulating the activator protein TopBP1. We found that DGD and OXA showed synergistic growth-inhibitory effects in liver cancer cells in vitro. DGD and OXA showed synergistic growth-inhibitory effects in liver cancer cells in vitro and showed lower cytotoxicity toward L-02 cells than an equi-effective higher concentration of OXA under the tested conditions in normal liver cells. The combination was associated with enhanced apoptosis, mitochondrial dysfunction, and oxidative stress. Further experiments suggested that DGD may enhance OXA-induced DNA damage, at least partly in association with suppression of ATR-related signaling. Consistent with the above results, DGD enhanced the antitumor efficacy of OXA in vivo without causing overt additional toxicity under the present experimental conditions.
Our findings indicate that DGD enhances the antitumor activity of OXA against liver cancer, with the in vitro synergistic effect being associated, at least partly, with suppression of ATR-related signaling, enhanced DNA damage, and oxidative stress. DGD also improved the antitumor efficacy of OXA in the xenograft model without overt additional toxicity.
Gardeniae Fructus (GF) is a well-known traditional Chinese medicine widely used in clinical prescriptions for its antidepressant, hepatoprotective, and other therapeutic effects. It contains multiple bioactive compounds, including iridoid glycosides, crocins, flavonoids, and organic acids. However, prolonged use or excessive doses of GF may lead to chronic or acute hepatotoxicity. This double-edged pharmacological profile has become a major obstacle to its clinical application. Accumulating evidence indicates that the gut microbiota plays a non-negligible role in the metabolism of traditional Chinese medicines. Notably, the dual effects of GF, both therapeutic and toxic, are closely associated with the microbial biotransformation of its active components, positioning the gut microbiota as a critical determinant of GF's efficacy and safety. Microbial enzymes may enhance the bioavailability and bioactivities of GF-derived ingredients, as well as generate novel metabolites with potential pharmacological activities. Concurrently, GF-induced alterations in bacterial composition may lead to changes in metabolic output, which further influence host physiological responses, thereby modulating the overall effects of GF. In this case, it is essential to incorporate gut microbiota–mediated bioactivities into the comprehensive evaluation of GF pharmacology. This review provides a comprehensive summary of the main bioactive compounds of GF and their biotransformation by the gut microbiota, and examines the dual effects of GF in the presence or absence of gut microbiota influences. Moreover, we discuss the potential of intestinal bacterial modulation as a strategy for balancing the efficacy and safety of GF. This review offers a thorough synthesis of the dual pharmacological actions of GF, while placing particular emphasis on the gut microbiota as a critical mediator of its divergent effects. We also offer new perspectives on the clinical potential of gut microbiota–targeted interventions to balance the dual effects of GF. The bidirectional crosstalk between gut microbiota and GF significantly influences the efficacy and toxicity of GF-derived compounds. Ecological management strategies may benefit the personalized treatment paradigm of GF, by accounting for interindividual variability in the gut microbiota.
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