ETHNOPHARMACOLOGICAL RELEVANCE:Squid ink has been documented in traditional Chinese medicine, notably in the ancient text Ben Jing, for its use in treating wounds, gastric disorders, and skin lesions, suggesting its potential as a source of bioactive compounds for dermatological applications. AIM OF THE STUDY:This study aimed to isolate and structurally characterize a novel polysaccharide from the ink of the cuttlefish Symplectoteuthis oualaniensis (SIP) and to evaluate its therapeutic potential and mechanism of action against atopic dermatitis (AD). MATERIALS AND METHODS:SIP was extracted, purified, and characterized using HPGPC, monosaccharide analysis, FT-IR, and NMR. Its effects were assessed in a TNF-α/IFN-γ-induced HaCaT keratinocyte inflammation model and a 2,4-dinitrochlorobenzene (DNCB)-induced murine AD model. Key markers of barrier function and inflammation were analyzed by qPCR, Western blot, and immunohistochemistry. The interaction with the mechanosensitive ion channel Piezo1 was investigated through molecular docking, dynamics simulations, calcium imaging, and functional assays. RESULTS:Structural analysis revealed SIP as a unique polysaccharide with a weight-average molecular weight of ∼30 kDa. In vitro, SIP significantly upregulated barrier proteins (filaggrin and involucrin) and suppressed pro-inflammatory cytokines (TSLP and IL-8). In AD-like mice, topical SIP application ameliorated clinical severity, restored epidermal integrity, reduced immune cell infiltration, and decreased levels of TSLP, TNF-α, IFN-γ, IL-4, and IL-13. Mechanistically, SIP directly bound to and inhibited Piezo1, thereby attenuating Ca2+ influx, NFAT1 nuclear translocation, and subsequent TSLP production. CONCLUSION:The polysaccharide SIP from squid ink exerts dual barrier-repair and anti-inflammatory effects in AD by targeting the Piezo1-Ca2+-NFAT1-TSLP axis. This work validates the ethnopharmacological relevance of a traditional marine resource and identifies a novel natural-product mechanism for ameliorating inflammatory skin disease.

Pain is a common symptom of many diseases and seriously affects the quality of life. Circadian rhythm is the regular, cyclical physiological, biochemical, and behavioral changes that occur within a 24-hour period in biological organisms, primarily regulated by clock genes. Pain sensitivity may have circadian rhythms, with clock genes likely influencing this pain-related rhythmicity. Therefore, restoring normal circadian rhythms and regulating the expression of clock genes are regarded as viable strategies to combat the development of pain. First, this review elucidates the core operational mechanisms of clock genes. Second, it also discusses the relationship among multiple types of pain and clock genes, such as sciatic nerve injury, inflammatory pain, chemotherapy-induced neuropathic pain, headache, the pain of Restless Legs Syndrome and fibromyalgia. Third, it presents the pain treatment and pain management strategies based on the current research on circadian rhythms. Exploring the role of circadian rhythm in pain can help increase our understanding of pain and have significant clinical implications for pain patients.

Natural bioactive pentacyclic triterpenoids, such as ursolic acid (UA), hold significant potential as anticancer agents. However, their clinical application is limited by their poor solubility and bioavailability. Herein, we developed a novel polypeptoid assembly cofactor-assisted nanoplatform designed to enhance UA's therapeutic efficacy through in situ self-assembly within the tumor microenvironment (TME). Bioactive polypeptoid polyelectrolytes, inspired by natural molecular chaperones, were utilized as assembly cofactors to guide UA's co-assembly into stimuli-responsive nanostructures. These polypeptoids provide precise control over the assembly process, improving stability and enabling reversible, pH-responsive transformations. Acid-responsive groups and the target molecule lactobionic acid further promote the specificity and efficacy of UA delivery. Under neutral conditions, the assemblies retain a helical fibrous structure, while in the acidic TME, they transform into virus-like clusters composed of assembly subunits, facilitating deeper tumor penetration. Once internalized, these nanoparticles escape into the cytoplasm and accumulate around the mitochondria, where the oxidation of thioether bonds triggers the release of UA and polypeptoids, causing mitochondrial damage and apoptosis. Some nanoparticles reassemble into fibrous structures intracellularly, extending their retention in tumor cells and potentially leading to mitochondria damage. Notably, the nanoplatform demonstrates excellent synergistic effects, achieving significantly higher therapeutic efficiency compared with individual components, including UA and polypeptoids. In vivo studies further confirmed the effectiveness, demonstrating significant tumor growth suppression and reduced metastasis. By integrating the therapeutic UA with bioactive polypeptoids under precise control, this synergistic platform represents a highly efficient and targeted approach to cancer therapy, offering a promising new opportunity for natural compounds for advanced nanomedicine.

ETHNOPHARMACOLOGICAL RELEVANCE:Rosemary (Rosmarinus officinalis L.) has been widely used as a traditional remedy for insomnia, depression and anxiety in China and Western countries. Modern pharmacological studies have shown that rosemary has important applications in neurological disorders. However, the mechanism of action of rosemary hydrosol in the treatment of insomnia is not known.AIMS OF THE STUDY:Insomnia is closely linked to anxiety and depression, and its pathogenesis is related to biology, psychology, and sociology. Rosemary is a natural plant that has been used to treat insomnia and depression and has good biological activity, but its material basis and mechanism for the treatment of insomnia are not clear. Here, we report on the role of aqueous extracts of rosemary in the treatment of insomnia.MATERIALS AND METHODS:The study was based on network pharmacology, using a combination of RNA-sequencing, "quantity-effect" weighting coefficients, and pharmacodynamic experiments. DL-4-chlorophenylalanine (PCPA) was intraperitoneally injected into SD rats to replicate the insomnia model with a blank, model, diazepam, and rosemary hydrosol low-, medium-, and high-dose groups were set up for the experiment. The key pathways in the treatment of insomnia with rosemary hydrosol were analyzed by molecular docking, open field assay, ELISA, western-Blot, Rt-PCR, and immunohistochemical assay.RESULTS:Rosemary hydrosol was analyzed by GC-MS to identify 19 components. 1579 differential genes were obtained by RNA-Seq analysis, 533 targets for rosemary hydrosol and 2705 targets for insomnia, and 29 key targets were obtained by intersection. The KEGG results were ranked by "quantity-effect" weighting coefficients, resulting in serotonergic synapse was the key pathway for the treatment of insomnia with rosemary hydrosol. Molecular docking results showed that 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, 3-methyl-4-isopropylphenol, caryophyllene, and citronellol of rosemary hydrosol acted synergistically to achieve a therapeutic effect on insomnia. Caryophyllene acts on the HTR1A target by upregulating 5-HT1AR, leading to increased 5-HT release, and upregulation of ADCY5, cAMP, PKA and GABAA at serotonergic synapses; citronellol upregulated ADCY5 and 1,7,7-trimethylbicyclo[2.2.1] heptan-2-one, and 3-methyl-4-isopropylphenol up-regulated GABAA to improve insomnia symptoms. In open-field experiments, ELISA kits (5-HT, GABA, and DA), Western-blotting, Rt-PCR and immunohistochemical assay experiments, insomnia rats in the low-, medium- and high-dose groups of rosemary hydrosol showed different degrees of improvement compared with the model group.CONCLUSIONS:It was shown that rosemary hydrosol may exert its therapeutic effects on insomnia through serotonergic synapses by combining RNA-Seq, "quantity-effect" weighting coefficients network pharmacology and pharmacodynamic experiments. We have provided a preliminary theoretical study for the development of rosemary hydrosol additive into a beverage for the treatment of insomnia, but it needs to be studied in depth. This study was conducted in rats and the results have limitations and may not apply to humans.

Atherosclerosis is an independent risk factor for cardiovascular diseases, which is related to dyslipidemia, endothelial injury, inflammation, thrombosis, dysfunction of vascular smooth muscle cells and macrophages, etc. Puerarin, a natural monomer from Chinese herb Pueraria lobata, presents multiple cardiovascular protective activities. The paper firstly reviewed the risk factors and drug of atherosclerosis. And then, extraction and synthesis of puerarin were summarized. Especially, it focused on the latest advances in anti-atherosclerosis activities of puerarin from six aspects including lipid-regulating, hyperglycemic, antiinflammatory, inhibiting thrombosis, promoting microcirculation, improving functions of vascular smooth muscle cells and macrophages. Some novel puerarin derivatives also exhibited favorable anti-atherosclerosis activity. The review would provide new molecular skeletons and lead compounds for anti-atherosclerosis new drug development based on puerarin.

川芎嗪又称四甲基吡嗪,是提取自伞形科藁本属植物川芎根茎的一种中药单体成分,属于酰胺类生物碱.川芎嗪除了具有传统的活血祛瘀、抑制血小板聚集、扩张血管、改善血液循环、缓解疼痛等作用外,随着研究的不断深入,发现川芎嗪还具有心脑血管疾病预防与治疗、多器官如心脏、脑组织和肾脏等的缺血再灌注损伤修复、血管内皮保护、肿瘤抑制、哮喘病人气道重塑、钙超载抑制和免疫调节等作用.现从川芎嗪在心血管疾病、脑疾病、肾损伤、肿瘤等疾病中的应用,对近几年川芎嗪最新研究进展进行综述,以期为川芎嗪的临床应用提供参考.

Age-related macular degeneration(ARMD)is one of the main causes of irreversible visual impairment in the middle-aged and elderly people, which severely impacts the patient's life quality and poses a substantial health economic burden on society. There are two types of late ARMD in clinic: wet ARMD and dry ARMD. Anti-vascular endothelial growth factor drugs, as first-line clinical drugs for wet ARMD, achieved remarkable efficacy. For dry ARMD, however, effective therapies are in the air. This review focuses on the potential drugs, biological therapies and traditional Chinese medicines that made significant progresses in clinical trials for dry ARMD, including anti-inflammatory drugs(doxycycline and FHTR2163), anti-oxidants(risuteganib and elamipretide), complement inhibitors(APL-2 and zimura), visual cycle modulators(ALK-001), neuroprotective agents(brimonidine), stem cell transplantation(MA09-hRPE and BMMF), gene therapy(HMR59), and traditional Chinese medicine(saffron, curcumin, quercetin and resveratrol). The new drugs exhibited favorable clinical efficacy and broad application prospects, which would foster hope for improvement and treatment of ARMD.

Malignant tumors seriously threaten people’s health and life worldwide. Natural products, with definite pharmacological effects and known chemical structures, present dual advantages of Chinese herbs and chemotherapeutic drug. Some of them exhibit favorable anti-cancer activity. Natural products were categorized into eight classes according to their chemical structures, including alkaloids, terpenoids and volatile oils, inorganic salts, phenylpropanoids, flavonoids and isoflavones, quinone, saponins and polysaccharides. The review focused on the latest advances in anti-cancer activity of representative natural products for every class. Additionally, anti-cancer molecular mechanism and derivatization of natural products were summarized in detail, which would provide new core structures and new insights for anti-cancer new drug development.

Matrine is an alkaloid extracted from traditional Chinese herbs including Sophora flavescentis, Sophora alopecuroides, Sophora root, etc. It has the dual advantages of traditional Chinese herbs and chemotherapy drugs. It exhibits distinct benefits in preventing and improving chronic diseases such as cardiovascular disease and tumors. The review introduced recent research progresses on extraction, synthesis and derivatization of Matrine. The summary focused on the latest research advances of Matrine on anti-atherosclerosis, anti-hypertension, anti-ischemia reperfusion injury, anti-arrhythmia, anti-diabetic cardiovascular complications, anti-tumor, anti-inflammatory, anti-bacterium, anti-virus, which would provide new core structures and new insights for new drug development in related fields.

心脑血管疾病是全球人类首要致死因素,动脉粥样硬化(As)是其主要病理基础.As发病机制复杂,临床使用的化学药物疗效单一,价格昂贵,不良反应较大.作用靶点多、不良反应少、价廉易得的中草药已成为防治心脑血管疾病的研究热点,丹参作为代表药物在As防治方面具有独特作用.该文章从中医与As关系以及丹参主要有效组分抗As活性方面,综述了丹参抗As的药理学研究进展,重点介绍了其水溶性组分丹酚酸B和丹酚酸A、脂溶性组分丹参酮ⅡA和隐丹参酮抗As活性与作用机制,以期为丹参抗As应用提供参考.

Diabetic retinopathy(DR)is a common chronic complication of diabetes mellitus, which cause irreversible damage of microvessels in the retina. DR is a leading blindness eye disease among diabetes mellitus. The pathogenesis of DR is mainly related to oxidative stress, inflammation and neovascularization. DR patients are treated with laser photocoagulation, vitrectomy and medicine in clinical trials. The traditional Chinese medicine and Chinese herb monomers have unique efficacy in the treatment of DR, especially in retinal protection, which provides valuable supplement. The paper summarized application practice and mechanism of representative Chinese herbal formulas and Chinese herb monomers in the treatment of DR, which would provide references for the clinical treatment and new drug development of DR.

心脑血管疾病为全球人类首要死因,动脉粥样硬化(As)是其主要病理基础.As发病机制复杂,与高血脂、高血糖、炎症、内皮损伤等密切相关.白藜芦醇(Res)是多酚类中药单体,具有良好的抗As活性,长期大量使用副作用较小.现综述Res的理化性质、提取、合成方法,重点介绍了Res通过改善血脂、抑制炎症、抗氧化、抑制血小板凝聚、降糖等途径改善As的作用,以期为Res的临床应用提供参考.

Glaucoma is an eye disease characterized by progressiveretinal nerve damage and impaired vision, which is the top one irreversible blinding eye disease. The pathologic intraocular pressure elevation is its key risk. At present, the clinical medicine with intraocular pressure reducing and retinal nerve protection effects focused on symptomatic therapy with unsatisfied effects. Chinese herb monomers have advantages of both Chinese herbs and chemical drugs. Chinese herbs and Chinese herb monomers have favorable effects on glaucoma therapy, especially on retinal nerve protection, which provides a vast room for new drug development. The paper summarized applications and mechanism of representative anti-glaucoma Chinese herbal formulas, Chinese herbs and especially Chinese herb monomers, which would provide references for clinical therapy and new drug development for glaucoma.