OBJECTIVE: To explore the mechanism by which the extract of Semen Ziziphi Spinosae extract promotes bone growth in mice by modulation of the expression of miR-34a-5p in brain tissue. METHODS: Mice were assigned to four experimental groups:a normal control group, a drug administration group (receiving 0.320 mg·g^-1 body weight of Semen Ziziphi Spinosae extract via intragastric administration), a positive control group (receiving 0.013 mg·g^-1 body weight of jujube seed saponin via intragastric administration), and a combination group administration with Semen Ziziphi Spinosae extract plus a 5-hydroxytryptamine 2A receptor (5-HT2AR) agonist (intragastric administration of Semen Ziziphi Spinosae extract combined with intracerebroventricular injection of 8 μg P-MPPF per mice for the final three days of the experiment). Following a 20-day administration period, the effects of the interventions on bone growth, serum growth hormone (GH) levels, and 5-HT2AR expression in brain tissue were evaluated. MicroRNAs (miRNAs) that were differentially expressed in the brain tissues of mice exhibiting bone growth induced by Semen Ziziphi Spinosae extract, as compared to those in normal mice, were identified using a gene chip approach. The interaction between miR-34a-5p and 5-HT2AR was subsequently validated through quantitative reverse transcription polymerase chainreaction (RT-qPCR) and dual-luciferase reporter gene assays. Subsequently, by utilizing the miR-34a-5p inhibitor group and mimics group, along with the normal control group, the drug administration group, the positive control group, and the drug administration combined with miR-34a-5p inhibitor group, the variations in 5-HT2AR expression in mouse brain tissue across all groups were examined, and the binding activity of 5-hydroxytryptamine (5-HT) to the 5-hydroxytryptamine 1A receptor (5-HT1AR) in mice was assessed. RESULTS: The body lengths of the normal control group and the drug administration group were(8.9±0.3) and(10.4±0.4) cm;femur lengths were (8.5±0.3) and (9.1±0.5) mm;tibia lengths were (10.7±0.3) and (11.2±0.4) mm, respectively. The contents of GH levels were (58.6±8.2) and (72.9±6.1) ng·ml-1;and the contents of 5-HT2AR were (32.0±5.0) and (21.9± 5.5) ng·ml-1, respectively. Compared with the normal control group, the drug administration group promoted the growth of body length, femur, and tibia in mice, and increased GH secretion, showing statistically significant differences (P<0.05). Additionally, it significantly reduced the content of 5-HT2AR in brain tissue, with statistical significance (P<0.01). The gene chip analysis identified a total of 16 differentially expressed miRNAs, of which 13 were up-regulated and 3 were down-regulated. Bioinformatics analysis predicted that the up-regulated miR-34a-5p could regulate the expression of 5-HT2AR, a prediction that was confirmed through a dual-luciferase reporter gene assay, demonstrating a direct regulatory interaction between the two. Furthermore, in vivo experiments in mice revealed that overexpression and silencing of miR-34a-5p resulted in corresponding changes in the expression levels of 5-HT2AR in brain tissues/cells, as well as in the binding activity between 5-HT and 5-HT1AR. CONCLUSION The Semen Ziziphi Spinosae extract promotes animal bone growth by enhancing miR-34a-5p expression in brain tissue, downregulating the expression level of 5-HT2AR, improving the binding activity between 5-HT and 5-HT1AR, and extending slow-wave sleep duration, thereby stimulating GH secretion.
Animals ; MicroRNAs/metabolism* ; Mice ; Male ; Brain/metabolism* ; Ziziphus/chemistry* ; Bone Development/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Plant Extracts/pharmacology*

OBJECTIVE: To explore the potential apoptotic mechanisms of 3 Morchella extracts (Morchella conica, Morchella esculenta and Morchella delicosa) on breast and colon cancer cell lines using apoptotic biomarkers. METHODS: Human breast cell line (MCF-7) and colon cancer cell line (SW-480) were treated with methanol and ethanol extracts of 3 Morchella species with concentration ranging from 0.0625 to 2 mg/mL. After that their effects on gene expression of apoptosis related markers (pro-apoptotic markers including Bax, caspase-3, caspase-7, and caspase-9, and the antiapoptotic marker including Bcl-2) were determined using reverse transcription polymerase chain reaction. RESULTS: All Morchella extracts reduced breast and colon cancer cells proliferation at half inhibitory concentration (IC₅₀) of 0.02 ±0.01 to 0.68 ±0.30 mg/mL. As expected, all Morchella extracts significantly increased gene expressions of Bax, caspase-3, caspase-7, and caspase-9 and downregulated the gene expression of Bcl-2 in MCF-7 and SW-480 cell lines (P<0.05). CONCLUSIONS Morchella extracts demonstrated significant anti-proliferative activity against breast and colon cancer cell lines via an apoptosis induction mechanism. Anticancer activity of Morchella extracts and activation of apoptosis in breast and colon cancer cells suggest that it may be used to develop chemotherapeutic agents against cancer in future.
Humans ; Apoptosis/genetics* ; Colonic Neoplasms/drug therapy* ; Breast Neoplasms/drug therapy* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Plant Extracts/pharmacology* ; Gene Expression Regulation, Neoplastic/drug effects* ; MCF-7 Cells ; Ascomycota/chemistry*

OBJECTIVE: To map the potent antifungal properties of the medicinal plant Vitex negundo, in vitro and in silico studies were performed to decipher the pharmacokinetics and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties of their phytoconstituents. METHODS: With the PASS (Prediction of Activity Spectra for Substances) prediction tool, many parameters of V. negundo phenolics were examined, including drug-likeness, bioavailability, antifungal activity, and anti-biofilm activity. Moreover, ADMET parameters were also determined. RESULTS: Eighteen phenolic compounds from V. negundo with significant antifungal activity against Candida species (human fungal pathogens) were detected. The antioxidant activity, inhibition percentage, and minimum inhibitory concentration value of V. negundo phenolic extracts indicate it as an effective antifungal agent for the treatment of candidiasis caused by the fungal pathogen Candida albicans. Many phenolic compounds showed a significantly high efficiency against Candida's planktonic cells and biofilm condition. CONCLUSIONS The phenolics fraction of V. negundo has potent antifungal activities, however, some more pre-clinical studies are a matter of future research to further investigate V. negundo phenolic compound as a potential new antifungal arsenal.
Candida albicans/physiology* ; Vitex/chemistry* ; Antifungal Agents/chemistry* ; Microbial Sensitivity Tests ; Biofilms/drug effects* ; Phenols/pharmacokinetics* ; Plant Extracts/chemistry* ; Antioxidants/pharmacology* ; Phytochemicals/pharmacology* ; Humans

OBJECTIVE: The present study investigated the cytoprotective effects of a Pogonatherum paniceum extract prepared with 80% ethanol (PPE) using synchrotron radiation-based Fourier transform infrared (SR-FTIR) microspectroscopy and determined its phytochemical profile. METHODS: The volatile and polyphenolic compounds in PPE were characterized using gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, respectively. The antioxidant capacity of PPE was evaluated using chemical and cell-based assays. The SR-FTIR microspectroscopy was performed to evaluate the cytoprotective effect of PPE by identifying changes in macromolecule composition in tert-butyl hydroperoxide (tBuOOH)-induced oxidative damage in RAW264.7 cells. RESULTS: A total of 48 volatile compounds and 28 polyphenol components were found in PPE. PPE exhibited a high potential for antioxidant activity by scavenging the intracellular reactive oxygen species in tBuOOH-induced oxidative damage in RAW264.7 cells. PPE treatment also significantly protected RAW264.7 cells against tBuOOH-induced toxicity and restored cell viability. The SR-FTIR analysis revealed that tBuOOH increased the lipid and ester lipid content in RAW264.7 cells. The PPE exerted a cytoprotective effect by decreasing the levels of lipid and ester lipid compounds that had been elevated by tBuOOH in RAW264.7 cells. These findings indicate that PPE has cytoprotective potential due to its ability to inhibit endogenous reactive oxygen species. CONCLUSION This study extends the current knowledge on the phytochemistry of PPE and its antioxidant and cytoprotective effects. These findings support the use of SR-FTIR microspectroscopy to determine the cytoprotective effects of natural products. PPE extract may be a candidate compound for new therapeutics and nutraceuticals that target the prevention of oxidative stress-associated diseases. Please cite this article as: Dunkhunthod B, Thumanu K, Teethaisong Y, Sittisart P, Sittisart P. Cytoprotective activity of Pogonatherum paniceum (Lam.) Hack. ethanolic extract evaluated by synchrotron radiation-based Fourier transform infrared microspectroscopy. J Integr Med. 2025; 23(2): 182-194.
Animals ; Mice ; Spectroscopy, Fourier Transform Infrared/methods* ; Plant Extracts/chemistry* ; RAW 264.7 Cells ; Synchrotrons ; Oxidative Stress/drug effects* ; Antioxidants/pharmacology* ; Ethanol/chemistry* ; Poaceae/chemistry* ; Cell Survival/drug effects* ; Cytoprotection/drug effects* ; Reactive Oxygen Species/metabolism* ; tert-Butylhydroperoxide

Metabolic syndrome (MetS) is a cluster of risk factors that significantly increase the chances of developing heart disease, type 2 diabetes mellitus, stroke, and other cardiovascular complications. Since current anti-MetS medications like statins, angiotensin-converting enzyme inhibitors, β-blockers, insulin sensitizers and diuretics have been reported to cause unwanted side effects, researchers are exploring promising alternatives. One such alternative relies on the potential of spices and condiments, which have a long history of use in traditional medicine. Among them, Cinnamomum zeylanicum Blume stands out as a popular spice worldwide for its unique taste, aroma, and delicate sweetness compared to other cinnamon varieties. This narrative review aims to summarize the in vivo and clinical evidence concerning the efficacy of C. zeylanicum against MetS indices. Relevant articles from PubMed, Scopus and Google scholar databases were reviewed. In vivo results suggested that C. zeylanicum preparations (extracts, essential oil, crude powder, bioactive compounds, and biosynthesized nanoparticles) were remarkably efficient in ameliorating MetS indices, while the clinical data were less and with several methodological limitations. Further robust clinical studies are warranted to definitively establish C. zeylanicum as a promising functional food for mitigating MetS, potentially leading to its dietary integration as a natural approach to improve metabolic health. Please cite this article as: Adarthaiya S, Arivarasan VK. Potential of Cinnamomum zeylanicum for metabolic syndrome management: insights from in vivo and human studies. J Integr Med. 2025; 23(3): 218-229.
Cinnamomum zeylanicum/chemistry* ; Humans ; Metabolic Syndrome/drug therapy* ; Plant Extracts/pharmacology* ; Animals ; Phytotherapy

Cynanchum atratum Bunge (C. atratum) and Cynanchum versicolor Bunge (C. versicolor) are two related species that have been used as "Baiwei" (Cynanchi Atrati Radix Et Rhizoma) in traditional medicine in China and other Asian countries for a long time. However, to date, no comprehensive review of C. atratum and C. versicolor has been published. This review provides a comprehensive summary on the botany, phytochemistry, traditional uses and pharmacology of Baiwei; The authors focus especially on the revision of errors in previous articles and reviews, updating information and providing a comparison of C. atratum and C. versicolor. Furthermore, current research reveals significant disparities in the chemical composition and pharmacological effects between C. atratum and C. versicolor. Up to November 2023, 178 compounds have been isolated from C. atratum and C. versicolor, including C₂₁ steroids, acetophenones, alkaloids and volatile oils. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-inflammatory, anti-tumor, anti-virus, anti-fungal, memory-enhancing and anti-pyretic action, immune modulatory effects, reducing blood lipid, inhibition of melanin production, and anti-parasitic effects. Therefore, this review presents new insights into these two herbs used as "Baiwei" and further study is warranted to enhance their clinical application. Please cite this article as: Xie W, Liu XY, Li X, Jin YS. Cynanchum atratum Bunge and Cynanchum versicolor Bunge for Baiwei: An updated review of their botany, phytochemistry, traditional uses and pharmacological activities. J Integr Med. 2025; 23(3): 230-255.
Cynanchum/chemistry* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Phytochemicals/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Plant Extracts/chemistry*

Nigella sativa L. seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo. This study revealed that the ethanolic extract of Nigella sativa L. (HZC) enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes. In accordance with established protocols, the ethanol fraction from Nigella sativa L. seeds was extracted, concentrated, and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, tyrosinase activity evaluation, measurement of cellular melanin contents, scratch assays, senescence-associated β-galactosidase (SA-β-gal) staining, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis for expression profiling of experimentally relevant proteins. The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr, Mitf, and gp100 in B16F10 cells. Furthermore, HZC effectively mitigated oxidative stress-induced cellular senescence, improved melanocyte condition, and rectified various functional impairments associated with melanocyte dysfunction. These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK, PKA, and Wnt signaling pathways. In addition, HZC attenuates oxidative damage induced by H₂O₂ therapy by activating the nuclear factor E2-related factor 2-antioxidant response element (Nrf2-ARE) pathway and enhancing the activity of downstream antioxidant enzymes, thus preventing premature senescence and dysfunction in melanocytes.
Oxidative Stress/drug effects* ; Melanocytes/cytology* ; Cellular Senescence/drug effects* ; Nigella sativa/chemistry* ; Plant Extracts/pharmacology* ; Seeds/chemistry* ; Mice ; Animals ; Melanins/metabolism* ; Monophenol Monooxygenase/metabolism* ; Humans

In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

A comprehensive phytochemical investigation of the leaves and twigs of Physalis angulata. var. villosa resulted in the isolation of 23 withanolide derivatives, including one novel 13,20-γ-lactone withanolide derivative (1) and three new withanolide derivatives (2-4). Architecturally, physalinin A (1) represents the first identified type B withanolide featuring a 13,20-γ-lactone moiety. The molecular structures of all isolates were elucidated using an integrated approach combining nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), infrared (IR) spectroscopy, and quantum chemical calculations to confirm structural assignments. The antiproliferative activities of all isolated withanolides were evaluated against four human cancer cell lines (HEL, HCT-116, Colo320DM, and MDA-MB-231). Among them, eight derivatives (2, 5-8, 14, 15, and 23) exhibited significant inhibitory effects, with half-maximal inhibitory concentration (IC₅₀) values of 0.18 ± 0.03 to 17.02 ± 0.21 μmol·L^-1. Structure-activity relationship (SAR) analysis suggested that the presence of an epoxide ring enhances anticancer activity, potentially through increased reactivity or specific interactions with molecular targets involved in cancer progression. These findings underscore the pharmacological potential of withanolides as promising lead compounds for the development of novel anticancer therapeutics.
Withanolides/isolation & purification* ; Physalis/chemistry* ; Humans ; Molecular Structure ; Cell Line, Tumor ; Antineoplastic Agents, Phytogenic/isolation & purification* ; Cell Proliferation/drug effects* ; Plant Leaves/chemistry* ; Plant Extracts/pharmacology*

Polycyclic polyprenylated acylphloroglucinols (PPAPs) represent a distinct subclass of specialized metabolites predominantly found in the plant kingdom, particularly within the Guttiferae (Clusiaceae) family. These compounds exhibit remarkable structural diversity and a wide range of biological activities. Seco- and nor-PPAPs, two unique variants of PPAPs with diverse skeletal structures, have been extensively investigated. As of June 2023, 200 compounds have been isolated from four genera, with Hypericum being the primary source. Notably, 115 of these compounds were identified in the past four years, indicating a significant increase in research activity. Seco- and nor-PPAPs can be categorized into six main subgroups based on the original PPAP scaffolds. Biological studies have revealed their potential in various therapeutic applications, including anti-cancer, anti-inflammatory, hepatoprotective, anti-Alzheimer's disease (anti-AD), multidrug resistance (MDR) reversal, anti-depressant, neuroprotective, and immunosuppressive effects. This review provides a comprehensive overview of the occurrence, structures, and bioactivities of natural seco- and nor-PPAPs, offering valuable insights for the further development of PPAPs.
Phloroglucinol/analogs & derivatives* ; Humans ; Molecular Structure ; Animals ; Clusiaceae/chemistry* ; Plant Extracts/pharmacology* ; Biological Products/pharmacology*