As the demand for safer and more natural skincare solutions grows, the fusion of ancient botanical wisdom with cutting-edge nanotechnology is unlocking unprecedented potential in skin therapeutics. Plant-based essential oils, long revered for their healing properties, have transcended traditional uses in massage and beauty treatments to emerge as powerful bioactive agents against microbial infections and skin disorders. However, their volatile nature and limited stability have posed significant challenges until now. This review explores the innovative field of essential oil nano-emulsions, in which natural substances are encapsulated within nanoscale systems to amplify their efficacy, stability, and skin penetration. Through in-depth investigation and comprehensive presentation, the presence of monoterpenoids that contribute to both the aroma and biological activities of essential oils is documented. The subsequent analysis introduces advanced methods used to create nano-emulsions containing essential oils, the pivotal role of surfactants, and the exceptional antimicrobial, anti-inflammatory, and wound-healing properties exhibited by these nano-emulsions. This is the first review that comprehensively presents essential oil nano-emulsions as a promising approach to address the imminent risks of skin infections and chronic wounds, thereby offering a bold new frontier in combating complex skin disorders. The future of skincare is unfolding, and it promises to be both natural and revolutionary.

The development of hepatocellular carcinoma (HCC) is a multistep process often associated with chronic hepatitis, liver fibrosis, and cirrhosis. Natural products, like resveratrol, have attracted considerable attention as anticancer drugs due to their diverse pharmacological activities. Resveratrol is a natural polyphenol present in plant foods, which has antioxidant, anti-inflammatory, anti-tumor, and anti-angiogenesis effects. The growing consensus shows that resveratrol plays a therapeutic role in liver diseases positively. The therapeutic effect observed in chronic hepatitis may be related to its ability to interfere with viral replication through PI3K/Akt, NF-κB, and MAPK signaling modulation, as well as to diminish hepatocellular injury by anti-inflammatory and antioxidant means. In liver fibrosis and cirrhosis, resveratrol decelerates the progression of fibrosis by suppressing the activation of hepatic stellate cells (HSC) and collagen production as well as by regulating signaling pathways, Hippo, Nrf2/Keap1, and SIRT1. Resveratrol also prevents tumor growth, induces apoptosis and inhibits migration, invasion and angiogenesis by various signaling pathways, which include PI3K/AKT, JNK, NF-κB, and p53 in advanced HCC. It is the first time that a multi-stage mechanism of resveratrol is presented in the development of HCC, which highlights its multi-target regulation and treatment capabilities.

Calycosin, a pivotal isoflavonoid active constituent derived from Astragalus membranaceus, is designated as a key marker compound for the quality assessment of Astragalus and its products in the Pharmacopoeia of the People’s Republic of China (2020 Edition). It exhibits a broad spectrum of pharmacological activities and holds significant potential for clinical application. This article systematically reviews the research progress on calycosin. In terms of extraction, isolation, and purification, techniques such as flash extraction and hydrolytic extraction enable efficient enrichment of the compound, whereas methods such as macroporous adsorption resin and high-speed counter-current chromatography allow for high-purity preparation. The biosynthetic pathways of calycosin encompass the phenylpropanoid pathway in planta, the chemical “one-pot” method in vitro, and synthesisvia microbial cell factories, offering diverse strategies for large-scale production. Structural derivatization, particularly through modification of the 7- and 3'-hydroxyl groups, significantly enhances its solubility and antitumor activity. With respect to pharmacological mechanisms, calycosin exerts multi-pathway and low-toxicity effects in diseases such as inflammation, cancer, and neural injury by modulating multiple signaling pathways, including NF-κB, PI3K/AKT, and MAPK. Furthermore, pharmacokinetic studies indicate that its absorption depends on deglycosylation, that it undergoes substantial hepatic first-pass metabolism, and that its tissue distribution is organ-specific. Safety evaluations suggest low toxicity at therapeutic concentrations. This review aims to clarify the core issues concerning the translation of basic research on calycosin into clinical practice, thereby providing a theoretical foundation for subsequent development.

Oncolytic peptides have emerged as a distinct class of antitumor agents with the potential to overcome therapeutic resistance and enhance anticancer immunity. Most oncolytic peptides are naturally derived or structurally inspired by natural peptides, and typically display cationic and amphipathic features. Mechanistically, these physicochemical properties enable preferential binding to the negatively charged membranes of cancer cells and subsequent membrane disruption. Beyond direct membrane lysis, many naturally derived oncolytic peptides (NDOPs) perturb intracellular organelle membranes, trigger immunogenic cell death, and modulate immune cells and immune checkpoints, thereby amplifying the cancer-immunity cycle. Through these multifaceted mechanisms, NDOPs show a low tendency to induce drug resistance and can enhance response rates when combined with conventional therapies. Notably, four NDOP-based agents have advanced into clinical trials, underscoring their translational promise. In this review, we summarize the sources, structural features, and mechanisms of NDOPs, highlight innovative therapeutic applications and rational combination strategies, and further discuss the current clinical progress. We also outline key challenges and future directions for the development of NDOPs as next-generation anticancer therapeutics.

Identifying novel therapeutic efficacies of traditional Chinese medicine (TCM) and their underlying mechanisms is essential for TCM modernization and development. Apocynum venetum leaf (AVL) is used both as an antihypertensive medicine and as a food. Whether AVL extract possesses additional therapeutic efficacies remains to be investigated. Here, we examined the potential effect of AVL extract on ameliorating postmenopausal osteoporosis (PMO) and identified the effective fractions and underlying mechanisms of its efficacy. We found that the total extract of AVL substantially relieved osteoporosis symptoms in both mouse and rat ovariectomized models. Moreover, the AVL-95% fraction, accounting for only about 2% of the total extract, exhibited a therapeutic effect on osteoporosis comparable to that of the total extract. Notably, the AVL-95% fraction improved both cancellous and cortical bones. Additionally, it exerted beneficial effects on both femurs and vertebrae in ovariectomized (OVX) mice. Mechanistic studies showed that AVL-95% inhibited osteoclastogenesis by suppressing RANKL signaling. Importantly, AVL-95% did not exhibit apparent toxicity in acute and chronic toxicity evaluations. Collectively, our work reveals a previously unknown efficacy of AVL in PMO intervention and an underlying mechanism of this efficacy, highlighting the anti-PMO application potential of AVL.

Diabetic kidney disease (DKD) is a major complication of diabetes mellitus, driven by hyperglycemia-induced oxidative stress, ER stress, and mitochondrial apoptosis. This study examined the protective effects of Morin against hyperglycemia-induced renal tubular injury, alone or in combination with the SGLT2 inhibitor Empagliflozin, with emphasis on the ATF6-DAPK1 axis. HK2 cells were exposed to high glucose with or without Morin and/or Empagliflozin. Cellular stress, mitochondrial function, and apoptosis were assessed. Morin-DAPK1 binding was examined via molecular docking, surface plasmon resonance (SPR), and cell thermal shift assay (CETSA). db/db mice received vehicle, Empagliflozin, Morin, or their combination for 14 weeks, followed by renal histological, biochemical, and metabolic evaluations. Morin reduced ROS accumulation, ER stress (p-PERK, p-eIF2α, CHOP, cleaved ATF6), mitochondrial dysfunction, and apoptosis in HK2 cells. It suppressed DAPK1 mRNA expression via ATF6 inhibition and directly bound DAPK1 (K _d = 1.61 μmol·L⁻¹), disrupting its interaction with pro-apoptotic BAK/BIK. Empagliflozin indirectly downregulated DAPK1 through ER stress relief. Combination therapy synergistically reduced oxidative stress, preserved mitochondrial membrane potential, and prevented apoptosis. In db/db mice, both compounds improved renal structure, lowered blood glucose, reduced UACR, and inhibited kidney stress markers, with greater improvements in the combination group, which also alleviated hepatic steatosis. Morin exhibits renoprotective effects against high glucose-induced cellular stress and diabetic kidney disease, at least partially via DAPK1 targeting. Co-administration with Empagliflozin enhances these effects, supporting its potential as an adjunct therapy for hyperglycemia-induced kidney injury.

Osteoporosis (OP) is characterized by impaired osteoblast activity and excessive bone resorption, yet effective anabolic therapies remain limited. Here, we identify heat shock cognate 71 kDa protein (HSC70) as a novel negative regulator of osteoblast differentiation and reveal echinacoside (ECH), a natural phenylethanoid glycoside from Cistanche deserticola, as its direct inhibitor. Functional studies demonstrated that inhibition or knockdown of Hsc70 promoted osteoblast differentiation and mineralization, while Hsc70 overexpression abrogated the effects of ECH. Mechanistically, ECH suppressed HSC70 activity to activate Wnt/β-catenin signaling, enhance β-catenin nuclear translocation, and improve mitochondrial dynamics, ATP production, and biogenesis, thereby providing metabolic support for osteogenesis. In vivo, ECH treatment and hsc70 knockout alleviated glucocorticoid-induced bone loss and restored mineralization in zebrafish models. Collectively, this work uncovers the HSC70–β-catenin/mitochondrial axis as a druggable pathway for skeletal homeostasis and positions ECH as a promising natural lead for developing bone-anabolic therapies against OP.

Coronary heart disease (CHD), characterized by impaired coronary artery function, often results in myocardial ischemia, hypoxia, and necrosis, with clinical manifestations such as angina pectoris. Vascular smooth muscle cell (VSMC) hypercontraction, primarily regulated by intracellular calcium (Ca²⁺), plays a central role in pathological coronary vasoconstriction. This study aimed to evaluate the therapeutic effects of Huatuo Zaizao Pills (HTZZ) in alleviating myocardial ischemia caused by abnormal coronary artery contraction and to elucidate the underlying molecular mechanisms. A double-blind, multicenter, randomized, placebo-controlled clinical trial was conducted to assess the efficacy of HTZZ in patients with angina pectoris. In vivo, pituitrin-induced acute myocardial ischemia mice and spontaneously hypertensive rats (SHRs) were used to evaluate myocardial and vascular responses to HTZZ. In vitro, vasorelaxation mechanisms were investigated using isolated rat mesenteric arterial rings, patch clamp, calcium imaging, and [³H]-ryanodine binding assays. HTZZ significantly reduced the frequency and duration of angina attacks in clinical settings. It improved myocardial ischemia in mice and enhanced vascular elasticity and diastolic function in SHRs. Mechanistically, HTZZ induced vasodilation by inhibiting extracellular Ca²⁺ influx and reducing intracellular Ca²⁺ levels via suppression of L-type calcium channels (LTCCs) and ryanodine receptors (RyRs). Long-term HTZZ administration also downregulated LTCC expression at both the protein and mRNA levels. HTZZ effectively alleviates angina and myocardial ischemia by suppressing Ca ²⁺-mediated vasoconstriction through targeting LTCCs and RyRs. These findings highlight HTZZ as a promising therapeutic candidate for CHD characterized by coronary vasospasm and ischemia.

Ras-GTPase activating protein SH3 domain-binding protein 1 (G3BP1), a core component of stress granules (SGs), is highly expressed in several liver diseases. SG assembly has also been observed in metabolic disorders, suggesting that this process may be a promising therapeutic target. Using a high-content drug screening approach based on G3BP1 expression, we identified Micranthin B (MB), a diterpenoid from Isodon lophanthoides (Buch.-Ham. ex D. Don) Hara, as a compound that alleviates metabolic dysfunction-associated steatohepatitis (MASH) by targeting G3BP1 and inhibiting SG formation. MB administration significantly alleviated MASH progression in both high-fat, high-cholesterol (HFHC) diet-induced mouse model and palmitic acid (PA)-stimulated hepatocytes. Mechanistically, MB inhibited histone deacetylase 6 (HDAC6)-mediated deacetylation of G3BP1, thereby suppressing SG formation. This prevented SG-mediated recruitment of the N-glycosylation-related proteins SEC61 translocon subunit beta (SEC61B) and calnexin (CANX), reduced the accumulation of misfolded or unfolded proteins, and alleviated endoplasmic reticulum (ER) stress. These findings suggest that MB has therapeutic potential in the treatment of MASH.