Online First List of Issues Document Types
Vol. 30 ， Issue 9 ， 2024
- Abstract：Objective:To confirm the efficacy and safety of Ganyushu Granule (GYSG) in treating premenstrual syndrome (PMS) in patients with Gan (Liver) depression and qi stagnation syndrome (GDQSS) and determine its effective dosage.Methods:From June 2018 to March 2021, a total of 240 PMS women with GDQSS were included and randomly divided into 3 groups in a 1:1:1 ratio using central block randomization: high-dose GYSG group (n=78, GYSG 2 packs/time), low-dose GYSG group (n=82, GYSG and its simulant 1 pack/time), and placebo group (n=80, GYSG simulant 2 packs/time). Treatment with GYSG or placebo was given thrice daily and for up to 3 menstrual cycles. Primary outcomes were PMS diary (PMSD) score and premenstrual tension syndrome self-rating scale (PMTS). Secondary outcomes were Chinese medicine (CM) syndrome efficacy. PMSD, PMTS, and efficacy of CM were evaluated with menstrual cycles during the treatment period. Outcome indicators were analyzed after each menstrual cycle. All analyses were performed using an intention-to-treat method, and clinical safety was assessed.Results:Of the 216 patients included in the effectiveness analysis, 70, 75, and 71 patients were in the high-, low-dose GYSG, and placebo groups, respectively. From the 2nd treatment cycle, the change in PMSD scores in the high- and low-dose groups was lower than that in the placebo group (P<0.05). PMTS scores in the high-dose GYSG group after the 1st treatment cycle was lower than that in the placebo group (P<0.05), while after the 3rd treatment cycle, that in the low-dose group was lower than that in the placebo group (P<0.05). After the 2nd treatment cycle, the high-dose GYSG group had the best CM syndrome efficacy (P<0.05). No serious adverse reactions were reported.Conclusions:GYSG was safe and well-tolerated at both doses for treating PMS patients with GDQSS. High-dose GYSG might be the optimal dose for a phase Ⅲ trial. (Registration No. ChiCTR1800016595)Keywords：premenstrual syndrome;Chinese medicine;Ganyushu Granule;randomized controlled trial
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Published：2024-08-24 - Abstract：Objective:To assess the efficacy and safety of Sanjie Analgesic Capsule (SAC) in Chinese patients with endometriosis-associated pain.Methods:This was a multicenter, randomized, double-blind, placebo-controlled trial conducted at 15 centers between November 2013 and July 2017 in China. Eligible 323 patients with endometriosis were randomized at a 3:1 ratio to the SAC group (241 cases) and placebo group (82 cases) by stratified block randomization. Patients in the SAC or placebo groups were given SAC or placebo 1.6 g 3 times per day, orally, respectively since the first day of menstruation for 3 consecutive menstrual cycles. The primary endpoint was clinical response to dysmenorrhea evaluated using a 10-point Visual Analogue Scale at 3 and 6 months. The secondary endpoint was the pain score evaluated by VAS (chronic pelvic pain, defecation pain, and dyspareunia) at 3 and 6 months, and the pain recurrence rate at 6 months. Adverse events (AEs) were recorded during the study.Results:A total of 241 women were included in the SAC group, and 82 were in the placebo group. Among these women, 217 (90.0%) and 71 (86.6%) completed the intervention, respectively. At 3 months, overall response rate (ORR) was significantly higher in women administered SAC (80.1%) compared with those who received a placebo (30.5%, P<0.01). Six months after treatment, the ORR for dysmenorrhea was 62.7% in the SAC group and 31.7% in the placebo group (P<0.01). Chronic pelvic pain and defecation pain were significantly improved by SAC compared with placebo (both P<0.05). The incidence rates of total AEs events in the SAC and placebo groups were 6.6% and 9.8%, respectively, and no significant difference was shown between the two groups (P=0.339).Conclusion:SAC is well-tolerated and may improve dysmenorrhea in women with endometriosis-associated pain. (Trial registration: ClinicalTrials.gov, No. NCT02031523)Keywords：endometriosis;pain;Sanjie Analgesic Capsule;randomized controlled trial;Chinese medicine
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Published：2024-08-24 - Abstract：Objective:To assess the effects of Thunbergia laurifolia L. extract (TLE) on gestational diabetes mellitus (GDM) in a rat model.Methods:Thunbergia laurifolin L. leaves were subjected to ethanolic extraction. In vivo study, 50 pregnant rats were randomly divided into 5 groups (10 for each): non-GDM group, GDM induced by streptozotocin (STZ, 60 mg/kg i.p.), metformin (MET) 100 mg/kg, TLE 50, and 500 mg/kg groups. Administration was performed on gestation day 7 until term (day 21). The effects of TLE on blood glucose, insulin levels, lipid profiles, liver enzymes, and maternal performances were assessed. In in vitro study, the effect of TLE was examined using the organ bath for uterine force measurement.Results:In in vivo study, TLE significantly reduced blood glucose as compared to GDM (P<0.05) with gradually increased insulin level. This effect was consistent with islets of Langerhans restoration. Histologically, the uterine muscular layer displayed a marked increase in fiber area in response to both doses as compared to GDM (P<0.05). Additionally, TLE significantly reduced total cholesterol, triglyceride, and alanine transaminase levels (P<0.05). Intriguingly, TLE also led to a notable augmentation in gravid uterus size, live fetuses count, and implantation numbers, while significantly reducing the post-implantation loss rate associated with fetal classification (P<0.05). Thus, GDM improvements were close to those produced by MET. In in vitro study, TLE exerted a concentration-dependent inhibition of spontaneous uterine contractility (half-maximal inhibition concentration=1.2 mg/L). This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated contractions. When combined with its major constituent, rosmarinic acid, TLE produced an enhanced inhibitory effect (P<0.05).Conclusions:TLE ameliorated blood glucose levels, enhanced uterine muscular structure, and improved maternal and fetal performance in GDM. TLE also displayed tocolytic properties. These findings underscore the need for further exploration of TLE as a potential tocolytic agent to mitigate GDM-associated complications.Keywords：myometrium;gestational diabetes mellitus;tocolytic;oxytocin;Thunbergia laurifolia L.
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Published：2024-08-24 - Abstract：Objective:To investigate whether Buthus martensii karsch (Scorpiones), Scolopendra subspinipes mutilans L. Koch (Scolopendra) and Gekko gecko Linnaeus (Gekko) could ameliorate the hypoxic tumor microenvironment and inhibit lung cancer growth and metastasis by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor-1α (PI3K/AKT/mTOR/HIF-1α) signaling pathway.Methods:Male C57BL/6J mice were inoculated with luciferase labeled LL/2-luc-M38 cell suspension to develop lung cancer models, with rapamycin and cyclophosphamide as positive controls. Carboxy methyl cellulose solutions of Scorpiones, Scolopendra and Gekko were administered intragastrically as 0.33, 0.33, and 0.83 g/kg, respectively once daily for 21 days. Fluorescent expression were detected every 7 days after inoculation, and tumor growth curves were plotted. Immunohistochemistry was performed to determine CD31 and HIF-1α expressions in tumor tissue and microvessel density (MVD) was analyzed. Western blot was performed to detect the expression of PI3K/AKT/mTOR/HIF-1α signaling pathway-related proteins. Enzyme-linked immunosorbent assay was performed to detect serum basic fibroblast growth factor (bFGF), transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF) in mice.Results:Scorpiones, Scolopendra and Gekko prolonged the survival time and inhibited lung cancer metastasis and expression of HIF-1α (all P<0.01). Moreover, Scorpiones, Scolopendra and Gekko inhibited the phosphorylation of AKT and ribosomal protein S6 kinase (p70S6K) (P<0.05 or P<0.01). In addition, they also decreased the expression of CD31, MVD, bFGF, TGF-β1 and VEGF compared with the model group (P<0.05 or P<0.01).Conclusion:Scorpiones, Scolopendra and Gekko all showed beneficial effects on lung cancer by ameliorating the hypoxic tumor microenvironment via PI3K/AKT/mTOR/HIF-1α signaling pathway.Keywords：Scorpiones;Scolopendra;Gekko;dredging collaterals and activating blood;Chinese medicine of worms;lung cancer;hypoxic tumor microenvironment;phosphoinositide 3-kinase/protein kinase B/ mammalian target of rapamycin/hypoxia-inducible factor-1α;signaling pathway
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Published：2024-08-24 - Abstract：Objective:To explore the effect of acupotomy intervention on autophagy of chondrocytes in rabbits with knee osteoarthritis (KOA), and to determine the possible mechanisms of acupotomy to alleviate cartilage degeneration.Methods:The modified Videman method was used to construct a KOA rabbit model. After modeling, 40 rabbits were randomly divided into 4 groups by a random number table: control; KOA (model); KOA + acupotomy (acupotomy), and KOA + sham acupotomy (sham), 10 in each group. After a 3-week treatment course, the knee joint activity was determined by the modified Lequesne MG index. Hematoxylin-eosin staining staining was used to examine the morphological changes of chondrocytes. Autophagy of chondrocytes was observed by transmission electron microscopy. The surface morphology of cartilage tissue was observed by scanning electron microscope. The mRNA and protein levels of AMP kinase/mammalian target of rapamycin/Unc-51 (AMPK/mTOR/ULK1) signal pathway key proteins, autophagy-related factor Beclin-1 and microtubule-associated protein 1A/1B light chain 3 (LC3) in rabbit knee cartilage were assessed by real-time fluorescence quantitative polymerase chain reaction and Western blot, respectively.Results:The modified Lequesne MG score of acupotomy group was significantly lower than that of model group (P<0.05). Pathological results showed that chondrocyte autophagy decreased and cartilage surface was rough in the model group, which recovered after acupotomy treatment. The mRNA expressions of AMPK, ULK1, Beclin-1 and the protein levels of p-AMPK, p-ULK1, Beclin-1, and LC3Ⅱ/LC3Ⅰ were decreased in the model group, while the mRNA and protein expressions of mTOR were increased (P<0.01). However, acupotomy treatment reversed these abnormal changes (P<0.05).Conclusions:Acupotomy could effectively up-regulate the expressions of AMPK, ULK1 and Beclin1, reduce the expression of mTOR, promote autophagy, and alleviate joint degeneration. Acupotomy is a promising complementary and alternative therapy for KOA.Keywords：acupotomy;knee asteoarthritis;autophagy;AMPK/mTOR/ULK1 signaling pathway;rabbit
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Published：2024-08-24 - Abstract：Objective:To explore the potential of metanephric mesenchymal cells (MMCs) for osteogenesis and naringin's ability to enhance this process and its molecular mechanism.Methods:Porcine MMCs at 70 days of gestation were used as tool cells, cultured in osteogenic induction medium, identified by immunocytochemistry staining. Osteogenic potential of porcine MMCs and naringin's ability to enhance this process was tested by detecting changes in cell viability, alkaline phosphatase (ALP) activity, the expression of runt-related transcription factor 2 (Runx2), osteopontin (OPN) and osteocalcin (OCN), and the formation of mineralized nodules, and the application of the p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin.Results:Immunocytochemical staining showed that the cells were Vimentin and Six2(+), E-cadherin and CK-18(–). Naringin can activate the p38 signaling pathway to enhance the osteogenesis of porcine MMCs by increasing cell viability, ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05). The application of p38 signaling pathway inhibitor SB203580 vitiated the osteogenesis-promoting effect of naringin, manifested by decreased ALP activity, the expressions of Runx2, OPN and OCN, and the formation of mineralized nodules (P<0.05).Conclusion:Naringin, the active ingredient of Chinese herbal medicine Rhizoma Drynariae for nourishing Shen (Kidney) and strengthening bone, enhances the osteogenic differentiation of renal MMCs through the p38 signaling pathway.Keywords：metanephric mesenchymal cells;naringin;osteogenesis differentiation
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Published：2024-08-24 - Abstract：Objective:To explore the potential mechanism of lysionotin in treating glioma.Methods:First, target prediction based on Bernoulli Naïve Bayes profiling and pathway enrichment was used to predict the biological activity of lysionotin. The binding between 5-lipoxygenase (5-LO) and lysionotin was detected by surface plasmon resonance (SPR) and molecular docking, and the inhibitory effects of lysionotin on 5-LO and proliferation of glioma were determined using enzyme inhibition assay in vitro and cell viability analysis, respectively. Furthermore, the pharmaceutical effect of lysionotin was explored by cell survival rate analysis and liquid chromatography with tandem mass spectrometry (LC-MS/MS). The protein expression, intracellular calcium ion concentration and cytoskeleton detection were revealed by Western blot, flow cytometry and fluorescence labeling, respectively.Results:Target prediction and pathway enrichment revealed that lysionotin inhibited 5-LO, a key enzyme involved in the arachidonic acid metabolism pathway, to inhibit the proliferation of glioma. Molecular docking results demonstrated that 5-LO can be binding to lysionotin through hydrogen bonds, forming bonds with His600, Gln557, Asn554, and His372. SPR analysis further confirmed the interaction between 5-LO and lysionotin. Furthermore, enzyme inhibition assay in vitro and cell survival rate analysis revealed that 50% inhibition concentration of lysionotin and the median effective concentration of lysionotin were 90 and 16.58 μmol/L, respectively, and the results of LC-MS/MS showed that lysionotin inhibited the production of 5S-hydroperoxy-eicosatetraenoic acid (P<0.05), and moreover, the LC-MS/MS results indicated that lysionotin can enter glioma cells well (P<0.01) and inhibit their proliferation. Western blot analysis demonstrated that lysionotin can inhibit the expression of 5-LO (P<0.05) and downstream leukotriene B4 receptor (P<0.01). In addition, the results showed that lysionotin affected intracellular calcium ion concentration by inhibiting 5-LO to affect the cytoskeleton, as determined by flow cytometry and fluorescence labeling.Conclusion:Lysionotin binds to 5-LO could suppress glioma by inhibiting arachiodonic acid metabolism pathway.Keywords：5-lipoxygenase inhibitor;lysionotin;5-lipoxygenase;leukotriene B4;calcium ion;cytoskeleton
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Published：2024-08-24
Original Article
- Abstract：As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed.Keywords：Cirsium;traditional use;antibacterial active components;bacteriostatic activity;bacteriostatic mechanism;Chinese medicine
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Published：2024-08-24
Herbal and Botanical Review
- Abstract：Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA.Keywords：rheumatoid arthritis;prevention;Chinese medicine;review
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Published：2024-08-24 - Abstract：Oral squamous cell carcinoma (OSCC) is the most common malignant cancer of the head and neck, with high morbidity and mortality, ranking as the sixth most common cancer in the world. The treatment of OSCC is mainly radiotherapy, chemotherapy and surgery, however, the prognosis of patients is still poor and the recurrence rate is high. This paper reviews the range of effects of natural medicinal plant active ingredients (NMPAIs) on OSCC cancer, including the types of NMPAIs, anti-cancer mechanisms, involved signaling pathways, and clinical trials. The NMPAIs include terpenoids, phenols, flavonoids, glycosides, alkaloids, coumarins, and volatile oils. These active ingredients inhibit proliferation, induce apoptosis and autophagy, inhibit migration and invasion of OSCC cells, and regulate cancer immunity to exert anti-cancer effects. The mechanism involves signaling pathways such as mitogen-activated protein kinase, phosphatidylinositol 3 kinase/protein kinase B, nuclear factor kappa B, miR-22/WNT1/β-catenin and Nrf2/Keap1. Clinically, NMPAIs can inhibit the growth of OSCC, and the combined drug is more effective. Natural medicinal plants are promising candidates for the treatment of OSCC.Keywords：natural medicinal plant;active ingredients;oral squamous cell carcinoma;mechanism;signaling pathway;review
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Published：2024-08-24
Review
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