BACKGROUND

Scabies is a highly contagious neglected tropical disease and a persistent challenge globally, particularly in regions like the Philippines, where it remains endemic. With conventional treatments facing limitations such as resistance and adverse effects, exploring the potential of traditional medicinal plants offers a promising avenue for novel therapeutics. However, evidence of their comparative efficacy and safety is still lacking.

To determine the efficacy and safety of Gliricidia sepium (kakawati), Senna alata (akapulko), and Tinospora rumphii (makabuhay) compared to topical scabicides or placebo in the treatment of Filipino patients with scabies using a systematic review. 

We searched the following databases from inception to March 2024: MEDLINE via PubMed, CENTRAL, EMBASE, EBSCO, HERDIN, ClinicalTrials.gov, WHO-ICRTP, and PHRR. We included all randomized controlled trials involving Filipino patients diagnosed with scabies where preparations containing one of three plants (G. sepium, S. alata, or T. rumphii) were compared with a topical scabicide or placebo for treatment. Two review authors independently applied eligibility criteria, assessed risk of bias (using Risk of Bias 2.0), and extracted data from the included studies. Primary outcomes were complete clearance of skin lesions, reduction of pruritus, and the presence of serious adverse events. Secondary outcomes were recurrence, any adverse events, adverse events requiring withdrawal, and patientreported outcomes. We used RevMan 5.4 to pool dichotomous outcomes using risk ratios and continuous outcomes using mean difference and applied random-effects meta-analysis. We tested for statistical heterogeneity using both the Chi2 test and the I2 statistic. We presented the results using forest plots with 95% confidence intervals. We intended to conduct a funnel plot analysis to check for reporting bias but were unable to because of the limited number of studies. Quality of evidence was assessed using the GRADE approach, and a Summary of Findings table was created using GRADEpro GDT for the primary outcomes.

We included nine RCTs (N=607 participants) that compared various dosage forms (ointments, lotions, poultice, soap, aqueous extract) containing one of the three plants (G. sepium, three studies; S. alata, two studies; T. rumphii, four studies) versus placebo or existing topical scabicides (permethrin, sulfur, crotamiton). Pooled analyses showed that there is probably no difference in complete clearance of lesions between G. sepium and 5% sulfur (RR 0.92 [0.79, 1.07], 2 RCTs, N=85, moderate certainty of evidence). We are uncertain about the difference in complete clearance of lesions between S. alata lotion and placebo (RR 4.94 [1.67, 14.62], 2 RCTs, N=157, very low certainty of evidence), T. rumphii and crotamiton (RR 1.02 [0.76, 1.37], 2 RCTs, N=131, very low certainty of evidence), and T. rumphii lotion and placebo (RR 5.28 [0.76, 36.43], 2 RCTs, N=71, very low certainty of evidence). Data could not be pooled for reduction in pruritus scores due to limited studies for each intervention. No serious adverse events were reported across all studies.

Gliricidia sepium (kakawati) is probably as effective and safe as 5% sulfur in the management of patients with scabies and may be a promising alternative herbal treatment. Future RCTs should compare it with scabicides recommended by the Philippine Department of Health and World Health Organization, such as permethrin, benzyl benzoate or oral ivermectin. T. rumphii and S. alata may also be investigated using RCTs that should be adequately powered and with good methodologic quality.

Cholangiocarcinoma (CCA) is a malignant tumor originating from cholangiocytes. However, it remains unclear about the pathogenesis of this carcinoma, which may be related to multiple factors. Currently, CCA is mainly treated by surgery, chemotherapy, and radiotherapy. Among them, surgery is the only potentially curative option for CCA. Nevertheless, the high malignancy and asymptomatic nature of CCA may lead to poor treatment outcomes. It has been demonstrated that Chinese medicine (CM) plays a significant role in various antitumor applications. Meanwhile, CM exhibits fewer side effects and high availability. Moreover, the in vitro application of CM monomers has been explored in many domestic and foreign studies. This article mainly reviews the signaling pathways and molecular mechanisms of CM monomers in the treatment of CCA in recent years. These findings are expected to provide new insights into the treatment of CCA.
Cholangiocarcinoma/drug therapy* ; Humans ; Drugs, Chinese Herbal/pharmacology* ; Bile Duct Neoplasms/drug therapy* ; Medicine, Chinese Traditional ; Animals ; Signal Transduction/drug effects*

OBJECTIVE: To explore the mechanism of action of asperosaponin VI (AVI) in the treatment of rheumatoid arthritis (RA) and validate it in ex vivo experiments using network pharmacology and molecular docking methods. METHODS: The predicted targets of AVI were obtained from PharmMaper, UniProt and SwissTarget Prediction platforms, the disease targets were collected from Online Mendelian Inheritance in Man, Therapeutic Target Database and GeneCards databases, the intersection targets of AVI and RA were obtained from Venny 2.1.0, and the protein-protein interaction (PPI) network was obtained from STRING database, which was analyzed by Cytoscape software and screened to obtain the core targets. Cytoscape software was used to analyze PPI network and screen the core targets. Based on the Database for Annotation, Visualization and Integrated Discovery database, Gene Ontology functional and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed, and Cytoscape software was used to construct the "Disease-Pathway-Target-Drug" network, which was finally verified by molecular docking and animal experiments. RESULTS: Network pharmacological studies showed that AVI was able to modulate 289 targets, with 102 targets for the potential treatment of RA, with the core pathway being the AKT/PI3K signaling pathway, and the core targets being the epidermal growth factor receptor (EGFR) and matrix metalloproteinase 9 (MMP9). Molecular docking results showed that AVI could produce strong binding with both of the 2 core targets. In vitro cellular experiments showed that AVI reduced nitric oxide, prostaglandin E₂, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1 β levels (P<0.05) and inhibited cyclooxygenase-2, nitric oxide synthase, EGFR, MMP9, phosphorylated phosphoinositide 3-kinase (p-PI3K), and phosphorylated serine-threonine kinase (p-AKT) proteins (P<0.05). The results of in vivo studies showed that AVI improved RA score and foot swelling thickness and decreased TNF-α, IL-6, p-PI3K and p-AKT levels in RA rats (P<0.05). CONCLUSION AVI exerts anti-inflammatory and anti-RA effects which might be related to the EGFR/MMP9/AKT/PI3K pathway.
Saponins/chemistry* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Matrix Metalloproteinase 9/metabolism* ; Protein Interaction Maps/drug effects* ; Humans ; Network Pharmacology ; Male ; Rats

OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

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: To evaluate the immediate effect of Kuanxiong Aerosol (KXA) on perioperative coronary microcirculation in patients with unstable angina (UA) suffering from elective percutaneous coronary intervention (PCI). METHODS: From February 2021 to July 2023, UA inpatients who underwent PCI alone in the left anterior descending (LAD) branch were included. Random numbers were generated to divide patients into the trial group and the control group at a ratio of 1:1. The index of coronary microcirculation resistance (IMR) was measured before PCI, and the trial group was given two sprays of KXA, while the control group was not given. IMR was measured again after PCI, cardiac troponin I (cTnI) and creatine kinase isoenzyme-MB (CK-MB) were detected before and 24 h after surgery, and major cardiovascular adverse events (MACEs) were recorded for 30 days. The data statistics and analysis personnel were blinded. RESULTS: Totally 859 patients were screened, and 62 of them were involved into this study. Finally, 1 patient in the trial group failed to complete the post-PCI IMR and was excluded, 30 patients were included for data analysis, while 31 patients in the control group were enrolled in data analysis. There was no significant difference in baseline data (age, gender, risk factors, previous history, biochemical index, and drug therapy, etc.) between the two groups. In addition, differences in IMR, cTnI and CK-MB were not statistically significant between the two groups before surgery. After PCI, the IMR level of the trial group was significantly lower than that of the control group (19.56 ± 14.37 vs. 27.15 ± 15.03, P=0.048). Besides, the incidence of perioperative myocardial injury (PMI) was lower in the trial group, but the difference was not statistically significant (6.67% vs. 16.13%, P=0.425). No MACEs were reported in either group. CONCLUSIONS KXA has the potential of improving coronary microvascular dysfunction. This study provides reference for the application of KXA in UA patients undergoing elective PCI. (Registration No. ChiCTR2300069831).
Humans ; Percutaneous Coronary Intervention ; Male ; Microcirculation/drug effects* ; Female ; Angina, Unstable/physiopathology* ; Pilot Projects ; Middle Aged ; Aged ; Drugs, Chinese Herbal/pharmacology* ; Aerosols ; Troponin I/blood* ; Coronary Circulation/drug effects* ; Elective Surgical Procedures

Peripheral nerve injury (PNI) encompasses damage to nerves located outside the central nervous system, adversely affecting both motor and sensory functions. Although peripheral nerves possess an intrinsic capacity for self-repair, severe injuries frequently result in significant tissue loss and erroneous axonal junctions, thereby impeding complete recovery and potentially causing neuropathic pain. Various therapeutic strategies, including surgical interventions, biomaterials, and pharmacological agents, have been developed to enhance nerve repair processes. While preclinical studies in animal models have demonstrated the efficacy of certain pharmacological agents in promoting nerve regeneration and mitigating inflammation, only a limited number of these agents have been translated into clinical practice to expedite nerve regeneration. Chinese herb medicine (CHM) possesses a longstanding history in the treatment of various ailments and demonstrates potential efficacy in addressing PNI through its distinctive, cost-effective, and multifaceted methodologies. This review critically examines the advancements in the application of CHM for PNI treatment and nerve regeneration. In particular, we have summarized the most commonly employed and rigorously investigated CHM prescriptions, individual herbs, and natural products, elucidating their respective functions and underlying mechanisms in the context of PNI treatment. Furthermore, we have deliberated on the prospective development of CHM in both clinical practice and fundamental research.
Drugs, Chinese Herbal/pharmacology* ; Humans ; Peripheral Nerve Injuries/drug therapy* ; Animals ; Nerve Regeneration/drug effects* ; Medicine, Chinese Traditional

OBJECTIVE: To assess the efficacy and safety of Erzhu Jiedu Decoction (EZJDD) Granules in treating mid-advanced hepatitis B virus-associated primary liver cancer (HBV-PLC) patients with Pi (Spleen)-deficiency and dampness-heat syndrome. METHODS: From January 2021 to June 2023, a cohort of 132 patients were enrolled and randomly assigned to a control group or a EZJDD group according to the random numbers, with 66 patients in each group. The patients in the control group received conventional treatment for 3 months, followed by a 3-month follow-up. In addition to the conventional treatment, patients in the EZJDD group were administered EZJDD Granules (10.9 g/pack, 2 packs twice per day) orally for same duration. Progression-free survival (PFS) as primary outcome was evaluated by Kaplan Meier method. Karnofsky performance status (KPS) scores were used to assess the quality of life in two groups before and after treatment, and survival rates were determined as well. The efficacy of Chinese medicine syndrome was calculated with Nimodipine method. Liver function, tumor indicators and T lymphocyte subsets were measured, respectively. Safety indicators were recorded and assessed. RESULTS: Of the 116 patients who completed the study, 57 were in the control group and 59 in the EZJDD group. The median PFS was 3.53 months (106 days) in the EZJDD group compared to 2.33 months (70 days) in the control group (P=0.005). Six-month survival rate was 52.63% (30/57) in the control group and 69.49% (41/59) in the EZJDD group (P=0.039). The median KPS score in the EZJDD group [70(63, 90)] was higher than that in the control group [70(60, 80)] (P=0.013). The total effective rate of CM syndrome was 52.63% (30/57) in the control group and 77.97% (46/59) in the EZJDD group (P=0.005). The levels of alpha fetoprotein, alpha fetoprotein-L3, alpha-L-fucosidase and protein induced by Vitamin K absence or antagonist- II in the EZJDD group increased less than the control group (P>0.05). CD8⁺ levels were decreased, while CD3⁺ and CD4⁺ levels, as well as CD4⁺/CD8⁺ ratio were significantly increased in the EZZJD group (P<0.05). No treatment-related adverse reactions were observed during the study. CONCLUSION EZJDD Granules significantly prolonged the median PFS and improved 6-month survival rate in patients with mid-advanced HBV-PLC (Registration No. ChiCTR2200056922).
Humans ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Liver Neoplasms/complications* ; Hepatitis B virus/physiology* ; Hepatitis B/complications* ; Treatment Outcome ; Adult ; Spleen/drug effects* ; Quality of Life ; Medicine, Chinese Traditional ; Aged ; Syndrome

OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To illustrate the role of dehydrocorydaline (DHC) in chronic constriction injury (CCI)-induced neuropathic pain and the underlying mechanism. METHODS: C57BL/6J mice were randomly divided into 3 groups by using a random number table, including sham group (sham operation), CCI group [intrathecal injection of 10% dimethyl sulfoxide (DMSO)], and CCI+DHC group (intrathecal injection of DHC), 8 mice in each group. A CCI mouse model was conducted to induce neuropathic pain through ligating the right common sciatic nerve. On day 14 after CCI modeling or sham operation, mice were intrathecal injected with 5 µL of 10% DMSO or 10 mg/kg DHC (5 µL) into the 5th to 6th lumbar intervertebral space (L5-L6). Pregnant ICR mice were sacrificed for isolating primary spinal neurons on day 14 of embryo development for in vitro experiment. Pain behaviors were evaluated by measuring the paw withdrawal mechanical threshold (PWMT) of mice. Immunofluorescence was used to observe the activation of astrocytes and microglia in mouse spinal cord. Protein expressions of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), phosphorylation of N-methyl-D-aspartate receptor subunit 2B (p-NR2B), and NR2B in the spinal cord or primary spinal neurons were detected by Western blot. RESULTS: In CCI-induced neuropathic pain model, mice presented significantly decreased PWMT, activation of glial cells, overexpressions of iNOS, TNF-α, IL-6, and higher p-NR2B/NR2B ratio in the spinal cord (P<0.05 or P<0.01), which were all reversed by a single intrathecal injection of DHC (P<0.05 or P<0.01). The p-NR2B/NR2B ratio in primary spinal neurons were also inhibited after DHC treatment (P<0.05). CONCLUSION An intrathecal injection of DHC relieved CCI-induced neuropathic pain in mice by inhibiting the neuroinflammation and neuron hyperactivity.
Animals ; Neuralgia/etiology* ; Mice, Inbred C57BL ; Analgesics/pharmacology* ; Neuroinflammatory Diseases/pathology* ; Constriction ; Male ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Nitric Oxide Synthase Type II/metabolism* ; Mice, Inbred ICR ; Microglia/pathology* ; Spinal Cord/drug effects* ; Female ; Mice ; Tumor Necrosis Factor-alpha/metabolism* ; Disease Models, Animal ; Constriction, Pathologic/complications* ; Interleukin-6/metabolism* ; Astrocytes/metabolism* ; Chronic Disease ; Neurons/metabolism*