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.

OBJECTIVE

Manihot esculenta (Crantz) leaves have been used for the management of diabetes based on cited ethnopharmacological studies. However, scientific evidence to support its efficacy is lacking. The aim of the study was to assess the cytotoxicity of the aqueous leaf extract and fractions of Manihot esculenta and its potential hypoglycemic effect on male Swiss albino mice.

The cytotoxicity assay was necessary to screen which extract and fractions will be used for the in vivo hypoglycemic study.

Phytochemical screening identified the composition of the aqueous crude extract and its fractions. The phytochemical results showed the presence of alkaloids, anthraquinone glycosides, carbohydrates, phenolic glycosides, saponins, and flavonoids.

Cytotoxicity was screened using CytoTox 96® (Promega), a NonRadioactive Cytotoxicity Assay on liver cancer (HepG2) and normal kidney (HK-2) cell lines. Five samples were tagged as highly cytotoxic and were flagged for further assays. These samples were DCM fraction (100 ppm), n-Hexane fraction (1 and 10 ppm), Ethyl acetate fraction (1 ppm), and Aqueous fraction (100 ppm).

The hypoglycemic activity was examined in alloxan-induced diabetic mice using in vivo hypoglycemic study. The aqueous crude extract at dose levels of 200 mg/kg and 300 mg/kg body weight showed significant reduction in blood glucose levels compared to the diabetic control but not exceeding the results in the metformin treatment group. A p-value of 0.05 set a priori was used to consider whether the intervention had a statistically significant difference compared to the diabetic control.

The effectiveness of aqueous crude extract in reduction of blood glucose in mice may be attributed to the synergistic effects of phytochemicals present, especially the alkaloids which were retained in the extract but were undetectable in the fractionated samples. The results of this study also support the findings of existing ethnopharmacological studies on M. esculenta leaf extract as a hypoglycemic agent.

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.

Background and Objective: Leptospirosis is a disease caused by pathogenic Leptospira prevalent in tropical countries like the Philippines. Some studies have shown that the role of currently used antibiotics for leptospirosis is unclear since trials have found no significant benefit to patient outcomes compared to placebo. This signals the need for alternative therapies, such as herbal medicines, which may provide effective therapeutic regimens in treating this infection. In this study, we characterized the antibacterial potential of three Philippine herbal medicines against Leptospira interrogans. Methods: Crude methanolic extracts of Momordica charantia, Cassia alata, and Allium sativum were subjected to an optimized broth microdilution assay against L. interrogans, utilizing the resazurin-resorufin reaction as a cell proliferation and viability indicator. Results: The respective minimum inhibitory concentrations of the plants were found to be as follows: 1.25 mg/mL (M. charantia), 2.5 mg/mL (C. alata), and >5 mg/mL (A. sativum). Conclusions Among the three herbal medicines, M. charantia and C. alata proved to have antibacterial activity against L. interrogans. Given the promising potential of two of these plant extracts, exploring the use of other solvents to extract natural compounds from these plants, and discovering possible synergistic effects between these plants and conventional antibiotics may be worthwhile.
Leptospira interrogans ; Herbal Medicine

Oleanolic acid (OA), a pentacyclic triterpenoid, exhibits a broad spectrum of biological activities, including antitumor, antiviral, antibacterial, anti-inflammatory, hepatoprotective, hypoglycemic, and hypolipidemic effects. Since its initial isolation and identification, numerous studies have reported on the structural modifications and pharmacological activities of OA and its derivatives. Despite this, there has been a dearth of comprehensive reviews in the past two decades, leading to challenges in subsequent research on OA. Based on the main biological activities of OA, this paper comprehensively summarized the modification strategies and structure-activity relationships (SARs) of OA and its derivatives to provide valuable reference for future investigations into OA.
Oleanolic Acid ; Structure-Activity Relationship ; Anti-Inflammatory Agents/pharmacology* ; Triterpenes ; Anti-Bacterial Agents/pharmacology*

Polysaccharides, predominantly extracted from traditional Chinese medicinal herbs such as Lycium barbarum, Angelica sinensis, Astragalus membranaceus, Dendrobium officinale, Ganoderma lucidum, and Poria cocos, represent principal bioactive constituents extensively utilized in Chinese medicine. These compounds have demonstrated significant anti-inflammatory capabilities, especially anti-liver injury activities, while exhibiting minimal adverse effects. This review summarized recent studies to elucidate the hepatoprotective efficacy and underlying molecular mechanisms of these herbal polysaccharides. It underscored the role of these polysaccharides in regulating hepatic function, enhancing immunological responses, and improving antioxidant capacities, thus contributing to the attenuation of hepatocyte apoptosis and liver protection. Analyses of molecular pathways in these studies revealed the intricate and indispensable functions of traditional Chinese herbal polysaccharides in liver injury management. Therefore, this review provides a thorough examination of the hepatoprotective attributes and molecular mechanisms of these medicinal polysaccharides, thereby offering valuable insights for the advancement of polysaccharide-based therapeutic research and their potential clinical applications in liver disease treatment.
Humans ; Drugs, Chinese Herbal/pharmacology* ; Liver Diseases/drug therapy* ; Antioxidants ; Polysaccharides/therapeutic use* ; Medicine, Chinese Traditional

Pathological vascular remodeling is a hallmark of various vascular diseases. Previous research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction, which leads to pathological vascular remodeling. Potassium dehydroandrographolide succinate (PDA), a derivative of andrographolide, has been clinically utilized in the treatment of inflammatory diseases precipitated by viral infections. This study investigates the potential of PDA in regulating pathological vascular remodeling. The effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 mice. Experimental approaches, including rat aortic primary smooth muscle cell culture, flow cytometry, bromodeoxyuridine (BrdU) incorporation assay, Boyden chamber cell migration assay, spheroid sprouting assay, and Matrigel-based tube formation assay, were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells (SMCs). Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein interactions. The results revealed that PDA exacerbates vascular injury-induced pathological remodeling, as evidenced by enhanced neointima formation. PDA treatment significantly increased the proliferation and migration of SMCs. Further mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88 (MyD88) expression in SMCs and interacted with T-cadherin (CDH13). This interaction augmented proliferation, migration, and extracellular matrix deposition, culminating in pathological vascular remodeling. Our findings underscore the critical role of PDA in the regulation of pathological vascular remodeling, mediated through the MyD88/CDH13 signaling pathway.
Mice ; Rats ; Animals ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Remodeling ; Cell Proliferation ; Vascular System Injuries/pathology* ; Carotid Artery Injuries/pathology* ; Molecular Docking Simulation ; Muscle, Smooth, Vascular ; Cell Movement ; Mice, Inbred C57BL ; Signal Transduction ; Succinates/pharmacology* ; Potassium/pharmacology* ; Cells, Cultured ; Diterpenes ; Cadherins

OBJECTIVE: To investigate the effects and underlying mechanisms of VX765 on osteoarthritis (OA) and chondrocytes inflammation in rats. METHODS: Chondrocytes were isolated from the knee joints of 4-week-old Sprague Dawley (SD) rats. The third-generation cells were subjected to cell counting kit 8 (CCK-8) analysis to assess the impact of various concentrations (0, 1, 5, 10, 20, 50, 100 μmol/L) of VX765 on rat chondrocyte activity. An in vitro lipopolysaccharide (LPS) induced cell inflammation model was employed, dividing cells into control group, LPS group, VX765 concentration 1 group and VX765 concentration 2 group without obvious cytotoxicity. Western blot, real-time fluorescence quantitative PCR, and ELISA were conducted to measure the expression levels of inflammatory factors-transforming growth factor β ₁ (TGF-β ₁), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α). Additionally, Western blot and immunofluorescence staining were employed to assess the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1). Thirty-two SD rats were randomly assigned to sham surgery group (group A), OA group (group B), OA+VX765 (50 mg/kg) group (group C), and OA+VX765 (100 mg/kg) group (group D), with 8 rats in each group. Group A underwent a sham operation with a medial incision, while groups B to D underwent additional transverse incisions to the medial collateral ligament and anterior cruciate ligament, with removal of the medial meniscus. One week post-surgery, groups C and D were orally administered 50 mg/kg and 100 mg/kg VX765, respectively, while groups A and B received an equivalent volume of saline. Histopathological examination using HE and safranin-fast green staining was performed, and Mankin scoring was utilized for evaluation. Immunohistochemical staining technique was employed to analyze the expressions of matrix metalloproteinase 13 (MMP-13) and collagen type Ⅱ. RESULTS: The CCK-8 assay indicated a significant decrease in cell viability at VX765 concentrations exceeding 10 μmol/L ( P<0.05), so 4 μmol/L and 8 μmol/L VX765 without obvious cytotoxicity were selected for subsequent experiments. Following LPS induction, the expressions of TGF-β ₁, IL-6, and TNF-α in cells significantly increased when compared with the control group ( P<0.05). However, intervention with 4 μmol/L and 8 μmol/L VX765 led to a significant decrease in expression compared to the LPS group ( P<0.05). Western blot and immunofluorescence staining demonstrated a significant upregulation of Nrf2 pathway-related molecules Nrf2 and HO-1 protein expressions by VX765 ( P<0.05), indicating Nrf2 pathway activation. Histopathological examination of rat knee joint tissues and immunohistochemical staining revealed that, compared to group B, treatment with VX765 in groups C and D improved joint structural damage in rat OA, alleviated inflammatory reactions, downregulated MMP-13 expression, and increased collagen type Ⅱ expression. CONCLUSION VX765 can improve rat OA and reduce chondrocyte inflammation, possibly through the activation of the Nrf2 pathway.
Rats ; Animals ; Chondrocytes/metabolism* ; Matrix Metalloproteinase 13/metabolism* ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism* ; Collagen Type II/metabolism* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; NF-E2-Related Factor 2/pharmacology* ; Inflammation/drug therapy* ; Osteoarthritis/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Dipeptides ; para-Aminobenzoates

OBJECTIVE: To Investigate the effects of lithocholic acid (LCA) on the balance between osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). METHODS: Twelve 10-week-old SPF C57BL/6J female mice were randomly divided into an experimental group (undergoing bilateral ovariectomy) and a control group (only removing the same volume of adipose tissue around the ovaries), with 6 mice in each group. The body mass was measured every week after operation. After 4 weeks post-surgery, the weight of mouse uterus was measured, femur specimens of the mice were taken for micro-CT scanning and three-dimensional reconstruction to analyze changes in bone mass. Tibia specimens were taken for HE staining to calculate the number and area of bone marrow adipocytes in the marrow cavity area. ELISA was used to detect the expression of bone turnover markers in the serum. Liver samples were subjected to real-time fluorescence quantitative PCR (RT-qPCR) to detect the expression of key genes related to bile acid metabolism, including cyp7a1, cyp7b1, cyp8b1, and cyp27a1. BMSCs were isolated by centrifugation from 2 C57BL/6J female mice (10-week-old). The third-generation cells were exposed to 0, 1, 10, and 100 μmol/L LCA, following which cell viability was evaluated using the cell counting kit 8 assay. Subsequently, alkaline phosphatase (ALP) staining and oil red O staining were conducted after 7 days of osteogenic and adipogenic induction. RT-qPCR was employed to analyze the expressions of osteogenic-related genes, namely ALP, Runt-related transcription factor 2 (Runx2), and osteocalcin (OCN), as well as adipogenic-related genes including Adiponectin (Adipoq), fatty acid binding protein 4 (FABP4), and peroxisome proliferator-activated receptor γ (PPARγ). RESULTS: Compared with the control group, the body mass of the mice in the experimental group increased, the uterus atrophied, the bone mass decreased, the bone marrow fat expanded, and the bone metabolism showed a high bone turnover state. RT-qPCR showed that the expressions of cyp7a1, cyp8b1, and cyp27a1, which were related to the key enzymes of bile acid metabolism in the liver, decreased significantly ( P<0.05), while the expression of cyp7b1 had no significant difference ( P>0.05). Intervention with LCA at concentrations of 1, 10, and 100 μmol/L did not demonstrate any apparent toxic effects on BMSCs. Furthermore, LCA inhibited the expressions of osteogenic-related genes (ALP, Runx2, and OCN) in a dose-dependent manner, resulting in a reduction in ALP staining positive area. Concurrently, LCA promoted the expressions of adipogenic-related genes (Adipoq, FABP4, and PPARγ), and an increase in oil red O staining positive area. CONCLUSION After menopause, the metabolism of bile acids is altered, and secondary bile acid LCA interferes with the balance of osteogenic and adipogenic differentiation of BMSCs, thereby affecting bone remodelling.
Female ; Mice ; Animals ; Core Binding Factor Alpha 1 Subunit/pharmacology* ; PPAR gamma/metabolism* ; Steroid 12-alpha-Hydroxylase/metabolism* ; Mice, Inbred C57BL ; Cell Differentiation ; Osteogenesis ; Mesenchymal Stem Cells ; Bile Acids and Salts/pharmacology* ; Bone Marrow Cells ; Cells, Cultured ; Azo Compounds

Humans ; Medicine, Chinese Traditional ; Bone Density ; Drugs, Chinese Herbal ; China