Journal of Herbmed Pharmacology
Volume:13 Issue: 2, Apr 2024

Over the past two decades, the secondary metabolite platform has determined the scientific direction of herbal medicines, while plant sources have been assumed to be the object of lead discoveries through bioassay-guided fractionation efforts. Nonetheless, the majority of purification programs have resulted in fractions and pure compounds with much lower efficacy than their parent extracts. It is then assumed that co-working action modes among chemical constituents occur in the herbal preparations. Primary metabolites (polysaccharides, peptides, and fatty acids) and mineral groups, on the other hand, have been neglected in the herbal effect contributions. This review aims to understand the interplay of secondary metabolites in herbal preparations, particularly how they interact with primary metabolites and mineral groups. Thus, by adhering to classical methods, it is possible to address certain aspects that modern standardization lacks, thereby facilitating a more comprehensive approach to these issues.

Autoimmune disease is a chronic condition that requires treatment with prolonged use of drugs. Consequently, there is a significant occurrence of adverse effects and toxicity associated with the medicine. On the other hand, epigallocatechin gallate (EGCG), the primary bioactive catechin in green tea (Camellia sinensis), has been demonstrated to possess anti-inflammatory properties and exhibit therapeutic effects in autoimmune disorders. Therefore, EGCG can be considered a complementary and alternative medicine to address the limitations of current treatment. Turning to the disease pathology, the balance between helper T-cell (Th) and regulatory T-cell (Treg) differentiation is the crucial aspect that needs to be regulated in order to attain immunological tolerance and suppress the incidence and severity of autoimmune disease. Here, we aim to comprehensively review the immunomodulatory effect of EGCG on the balance of Th/Treg cell differentiation in diverse autoimmune disorders. Scientific databases, including Scopus, PubMed, Science Direct, and Google Scholar, were searched using the keywords autoimmune AND (epigallocatechin-3-gallate OR epigallocatechin gallate OR EGCG) AND (Thelper OR Th OR Treg OR CD4). Our review revealed that EGCG has ability to repair the imbalance of Th/Treg cell differentiation in rheumatoid arthritis (RA), multiple sclerosis (MS), ulcerative colitis (UC), and autoimmune uveitis (AU) by inhibiting the differentiation of Th1 and Th17 cells while promoting the differentiation of Th2 and Treg cells, as well as improving the clinical conditions of the tested animals. Hence, it might be inferred that EGCG exhibits considerable promise as a viable complementary and alternative therapeutic option for autoimmune disease.

Fucoidan, produced by the cell walls of brown seaweed, possesses biological effects, covering anticancer, antiviral, anti-inflammatory, antioxidant, and a potential for promoting angiogenesis and osteogenesis. This study aimed to compile diverse scientific results on fucoidan’s therapeutic prospect in dentistry and the mechanism of action in the therapy of oral diseases. A literature search was carried out using keywords with Boolean operators, including fucoidan (AND) oral (OR) dental (OR) dentistry, to identify related publications from PubMed, ScienceDirect, and Google Scholar databases. The results showed that fucoidan had various therapeutic potentials in the field of dentistry, including anticancer, anti-inflammatory, radioprotection, protection of dental pulp tissue, and bone regeneration. These characteristics were related to the sulfate composition and molecular weight. Fucoidan has various therapeutic potentials crucial for oral health. Hence, it might be used for material development and drug production in dentistry

Ampelocissus africana is a medicinal plant used to treat several diseases, including those affecting the prostate. This study investigated the effects of the aqueous extract of rhizomes from Ampelocissus africana (AAA) on a testosterone propionate (TP)-induced benign prostatic hyperplasia (BPH) model.

The effect of the extract at 50, 150, and 300 mg/kg on BPH in male rats was assessed using daily subcutaneous injections of 3 mg/kg TP for four consecutive weeks. After the induction schedule, physical parameters, prostate index (PI), serum biochemical parameters, homogenate antioxidant, enzyme parameters, and prostates histopathological studies were carried out. Triterpenes and sterols were also assessed.

Treatment with AAA reduced the PI level in a dose-dependent manner (up to 75.91% at the dose of 300 mg/kg). The inflammatory marker measured in the present study, namely C-reactive protein, increased significantly in the BPH group and improved with the treatments. In addition, AAA reduced oxidative stress by decreasing the malondialdehyde (MDA) level and increasing the catalase (CAT) and superoxide dismutase (SOD) levels in comparison to the positive control group. A histopathological examination corroborated the result of the analysis of the physical and biochemical parameters. The study also showed interesting levels of triterpenes (119.5 ± 4.5 mg UAE/g) and sterols (104.6 ± 3.06 mg CE/g).

These results suggest that the aqueous extract of Ampelocissus africana could be used as a natural herbal therapy to treat BPH.

 Combretum aculeatum is a plant of Combretaceae family. In traditional medicine, it is used to treat schizophrenia. The aim of this study was to assess the possible impacts of hydroethanolic extract of C. aculeatum root bark on D-galactose (D-Gal)-induced amnesia in mice.

Memory was tested using Y-maze test, radial arms maze (RAM), and new item appreciation. Mice brains were collected for histological and biochemical testing.

 Combretum aculeatum substantially (P < 0.001) improved the ratio of spontaneous alternation versus negative control. In addition, discrimination index, and the time required to appreciate the new item were reversed considerably (P < 0.001) in mice receiving the extract opposed to the negative control fraction in the novel object appreciation test. The frequency of working memory mistakes was reversed in receiving extract categories versus negative control animals in RAM essay. Various doses of the extract substantially (P < 0.001) diminished the level of malondialdehyde (MDA), and crucially enlarged superoxide dismutase (SOD) and catalase activity as opposed to the negative control. Furthermore, all doses of the extract had a restructuring effect on the organization of hippocampal cells.

 Combretum aculeatum improved cognitive impairment possibly thought its antioxidant activity.

Metabolic syndrome is multifaceted health condition associated with metabolism, which leads to the accumulation of oxidation products and impairment of the antioxidant system. Medicinal, edible plant alternatives are being sought to prevent the predisposing factors of metabolic syndrome, one of which is obesity. We studied the effects of hydroethanolic garlic extract (HGE) on oxidative stress, lipolysis, and glycogenesis in high-fat diet-fed Drosophila melanogaster.

The HGE was processed and antioxidant assays (in vitro and in vivo) coupled with metabolic biomarkers were assayed following standard procedures.

HGE inhibited ABTS (2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), hydroxyl, and hydrogen peroxide radicals in high-fat-fed D. melanogaster. The HGE also reduced the activity of superoxide dismutase and increased catalase activity significantly. The HGE promoted lipolysis and glycogenesis by reducing cholesterol, triglycerides, and total sugar concentrations while glycogen content was increased.

Our results revealed that HGE improved the antioxidant defense system and promoted lipolysis and glycogenesis in metabolic deranged D. melanogaster. This suggests the therapeutic usefulness of garlic in the management of metabolic diseases.

 Olax subscorpioidea is a medicinal plant that Africans use to treat numerous ailments, including cancer. This research examines the antioxidant, anticancer, and in-silico properties of ethyl acetate fraction of Olax subscorpioidea’s (OSEA) on 7,12-Dimethylbenz(α) anthracene (DMBA)-induced cell proliferation in female rats.

Forty female Sprague Dawley rats averaging 110 ± 20 g were induced proliferation with DMBA (80 mg/kg) and treated with ethyl acetate fraction (250 mg/kg BW) of O. subscorpioidea or tamoxifen (6.6 mg/kg BW) before and after induction. The trial lasted 22 weeks. In-vivo antioxidant parameters such as superoxide dismutase (SOD), malondialdehyde (MDA), and reduced glutathione (GSH) were examined. Likewise, carcinoma antigen marker (CA153), and DNA methyltransferase 3-like (DNMT3L) activity were measured. Gas chromatography-mass spectrometry (GC-MS) detected the bioactive compounds, and molecular docking studies predicted the mechanism of action of OSEA against DNA methyltransferase.

Treatment with OSEA significantly increased the SOD activity, enhanced GSH levels, and lowered the levels of MDA, CA-153, and DNMT3L in DMBA-exposed rats. The GC-MS analysis of OSEA revealed the presence of 40 bioactive compounds. The molecular docking revealed that 4-cyclopentene-1,3-dione (-6.407 kcal/mol), 2-(2-hydroxyethylthio) (-4.926 kcal/mol) and 3,4,5,6-tetrahydrophthalic anhydride (-6.16 kcal/mol) had the lowest binding energies against DNMT1, DNMT3A, and DNMT3B, respectively. 2-(2-hydroxyethylthio) was the least toxic. The molecular dynamic simulation revealed that the interaction between DNMT3A and 2-(2-hydroxyethylthio) propionic was stable to an extent.
The in-silico and biochemical analysis of the ethyl acetate fraction of O. subscorpioidea showed that it can protect against lipid peroxidation and oxidative stress and may be a potent source of drug that serves as an effective therapeutic in the future.

 Muntingia calabura is a medicinal plant possessing antimicrobial properties against various bacteria. The purpose of this study was to examine in vitro and in silico activity of the ethyl acetate fraction of M. calabura leaves against the acne-causing commensal bacterium, Staphylococcus epidermidis.

In this study, M. calabura leaves were extracted using ethanol and then further fractionated with ethyl acetate. The phytochemicals in the fraction were identified with thin layer chromatography (TLC). The activity of the fraction was then tested in S. epidermidis culture using the agar diffusion method. Additionally, the molecular docking of M. calabura phytochemicals constituents was simulated to teicoplanin-associated locus regulator (TcaR) of S. epidermidis.

The ethyl acetate fraction of M. calabura exhibited robust antibacterial activity against S. epidermidis culture, resulting in inhibition zones ranging from 5 to 10 mm. The fraction was found to contain flavonoids, saponins, and tannins as identified constituents. Further, during the molecular docking analysis, stigmasterol and 7-methoxyflavone demonstrated binding to TcaR with a lower and comparable binding energy of -7.40 and -6.19 kcal/mol, respectively, compared to the control drug, Penicillin-G (-6.40 kcal/mol).

 M. calabura has the potential to serve as a valuable source of active phytochemical compounds for addressing acne. Further studies are needed to isolate and evaluate each compound found in M. calabura individually against S. epidermidis.

Yam bean (Pachyrhizus erosus L.) offers numerous health benefits. However, the effects of its dietary fiber (yam bean fiber, YBF) on dyslipidemia, liver disease, and the overproduction of metabolic hormones, specifically glucagon-like peptide-1 (GLP1) and fibroblast growth factor 21 (FGF21), resulting from a high-fat diet (HFD) remain underexplored. Thus, our present investigation sought to address this gap.

Adult male mice (n = 24) were randomly assigned into four different groups such as normal diet (ND) as a control group, HFD, and HFD supplemented with either 2.5% or 10% YBF. After a 12-week dietary regimen, plasma lipid profiles, liver histology and biochemistry, and the levels of FGF21 and GLP-1 were assessed.

YBF supplementation, especially at 10% dose, effectively lowered total serum cholesterol, triglyceride (TG), and low-density lipoprotein (LDL) compared with those fed HFD (P < 0.05). YBF also reduced liver weight and mitigated the elevation of malondialdehyde (MDA) and the depletion of catalase (CAT) activity induced by HFD in liver tissues (P < 0.05). Furthermore, 10% YBF supplementation effectively countered liver pathology, including central vein enlargement, hepatic steatosis, inflammation, abnormal sinusoids, and hepatocyte degeneration caused by HFD (P < 0.05). YBF at 10% also attenuated the HFDinduced hypersecretion of FGF21 and GLP-1 hormones.

Our findings indicate that YBF supplementation could counteract the adverse effects of HFD, particularly in terms of dyslipidemia, liver disease, and metabolic hormone imbalances. Incorporating YBF into diets may thus offer protective benefits against HFDinduced metabolic diseases and associated health issues.

This research explores the capability of silver nanoparticles (AgNPs) produced via friendly methods by using Solanum trilobatum leaf extract. The choice of S. trilobatum was supported by its diverse phytochemical makeup, which comprises recognized bioactive elements known for their anti-inflammatory and anti-cancer attributes. This research explores the effect of AgNPs derived from this plant as a promising eco-friendly strategy in oral cancer treatment.

The synthesis of AgNPs involved employing S. trilobatum leaf extract, with observable color changes and spectral analyses confirming the unique characteristics of the nanoparticles. Fourier transform infrared spectroscopy detected distinct functional groups, whereas scanning electron microscopy (SEM) confirmed the presence of biocapped nanoparticles exhibiting various shapes and sizes spanning from 100 to 300 nm.

Cytotoxicity assessments via the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay revealed a half-minimal inhibitory concentration (IC50) value of 3.715 ± 0.242 μg/mL against the oral cancer (KB) cell line, indicating a significant inhibition. Acridine orange/ethidium bromide (AO/EtBr) and reactive oxygen species (ROS) assays further supported the AgNPs’ anti-cancer potential, affirming their promise for oral cancer therapy.

AgNPs synthesized from S. trilobatum leaf extract showed substantial potential as a therapeutic agent for oral cancer. This research adds to the increasing evidence endorsing the use of environmentally friendly synthesized nanoparticles in medical treatments.

Melanin is a defense against UV radiation; however, it leads to significant cosmetic issues mainly melasma and hyperpigmentation. This study evaluated the potential effect of ethyl acetate (EtOAc) fraction of Centella asiatica extract in vitro inhibition activity against tyrosinase (TYR). Bioinformatics and in silico experiments were also employed to predict molecular pathways of asiaticoside, as the main active compound.

 Centella asiatica was extracted with ethanol and then fractionated with EtOAc. The fraction was tested in vitro for TYR inhibitory activity, and its active compounds were investigated using thin-layer chromatography (TLC). After obtaining the online database of the genes related to pigmentation and melanogenesis in the skin, the genes affected by asiaticoside were determined by the Venn diagram. The top 10 target proteins, underlying molecular pathways, got from CytoHubba, were further studied to figure out their molecular pathway. The molecular docking was conducted on two selected protein targets.

EtOAc fraction of C. asiatica extract demonstrated strong TYR inhibitory activity with an IC50 of 18.85 μg/mL. TLC profiling of the EtOAc fraction revealed the Rf value of 0.28 for the standard, Rf value of 0.26, 0.21, and 0.15 for the extract, and Rf value of 0.26 and 0.15 for the fraction. Asiaticoside inhibited melanogenesis by elaborating many molecular pathways involving keratinocytes, melanocytes, fibroblast, and endothelial cells by elaborating cytokine, growth factor, extracellular matrix, and melanin degradation enzyme

Asiaticoside-rich C. asiatica fraction has the potential as an anti-melanogenesis agent through its TYR inhibitory activity and many molecular pathways.

The use of Securidaca longipedunculata for solving health problems related to immunological disorders is long-standing. The immunomodulatory activity associated with the anti-inflammatory effect of S. longipedunculata has not yet been elucidated by scientific research. The aim of our study is to show that the leaves of S. longipedunculata can solve problems related to immunodeficiency and inflammation.

The phytochemical compounds of the plant were carried out by solubility tests. The anti-inflammatory activity of the plant was evaluated by the chicken egg albumin denaturation inhibition, membrane stabilization, and C-reactive protein (CRP) tests. The 2,2-diphenyl1-picrylhydrazyl, total antioxidant capacity, and inhibition of lipoperoxidation tests were performed to evaluate the antioxidant activity of the plant. Immunosuppression was induced in rats by cyclophosphamide. The immunomodulatory activity of S. longipedunculata was studied by blood count. The lactate dehydrogenase (LDH) titration showed the effect of S. longipedunculata on the energy balance.

The extract contained polyphenols, flavonoids, and tannins. The tests of albumin denaturation inhibition, membrane stabilisation, CRP, total antioxidant capacity, and 2,2-diphenyl-1-picrylhydrazyl revealed that the extract had anti-inflammatory and antioxidant effects. The blood count results revealed that the extract non-significantly increased the number of leukocytes except in the case of neutrophils and monocytes at a dose of 400 mg/kg (P<0.05). The extract also restored the energy balance in the rats according to the LDH results.

This study reveals that the hydro-ethanolic extract of S. longipedunculata leaves has potential immunostimulant and anti-inflammatory effects.

Diabetic foot ulcer (DFU) potentially leads to loss of function, infections, hospitalization, lower-extremity amputation, and even death. The potential therapeutic efficacy of a polyherbal candidate named TIP-Heal was identified for treating DFU. TIP-Heal, which stands for Tinospora crispa, Isotoma longiflora, and Piper betle L var nigra, consists of extracts from these three herbs in a ratio of 2:1:1. The Indonesian population commonly uses these herbs due to their wound-healing properties. It is our interest to analyse the mechanism of the polyherbal extract using network pharmacology and molecular docking.

This study uses network pharmacology and molecular docking methods to analyze the multi-target mechanism of active compounds in TIP-Heal extract for DFU treatment. The proteins targeted by the bioactive chemical present in TIP-Heal and DFU were identified within a particular dataset with the keyword “homo sapiens.” The identified target proteins were assessed using gene ontology (GO) analysis, the Kyoto Encyclopaedia of Gene and Genomes (KEGG) pathways, protein-protein interactions (PPIs), and molecular docking.

The critical proteins obtained were AKT serine/threonine kinase 1 (AKT1), caspase-3 (CASP3), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and matrix metalloproteinase-9 (MMP-9). Several compounds, namely PubChem (Compound Identifier=CID: 5319898), 3-epiursolic acid, palmitic acid, and alpha-linolenic acid showed great potential as viable candidates to facilitate the healing process of DFU.

The findings of this study indicate that the TIP-Heal extract has the potential to be used as a natural herbal treatment for DFUs with the involvement of AKT1, CASP3, EFGR, and SRC proteins.

Oral cancer’s aggressive nature poses a significant health risk, demanding timely diagnosis and effective treatment. Despite progress in conventional therapies like chemotherapy and surgery, their limitations drive the exploration of alternative strategies. This study assessed Solanum trilobatum-derived silver nanoparticles (AgNPs) in impacting cancer cell cycles, inducing apoptosis, and modulating key pathways, including the phosphoinositide 3-kinase (PI3K)/Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway, leveraging phytotherapy and nanotechnology—a promising frontier in cancer treatment.

AgNPs were synthesized through the reduction of ions and stabilized using aqueous leaf extracts of S. trilobatum. After the characterization of AgNPs, the mRNA Gene Expression and mitochondrial membrane potentials (MMPs) were assessed. DNA fragmentation was done and DNA pattern by gel documentation system was observed. The study also assessed the modulation of the PI3K/Akt/mTOR cascade, impacting tumor growth and proliferation.

Biosynthesized AgNPs were characterized using UV-visible spectrophotometry (UVvis), energy-dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and Fourier-transform infrared (FTIR) spectroscopy. DNA fragmentation exhibited a typical ladder pattern. Dose-dependent changes in MMP were observed in the treated oral cancer cells. The effect of S. trilobatum-derived AgNPs in targeting the cell signaling pathway correlated significantly with their anticancer potency (P<0.001).

This study reveals S. trilobatum leaf extract-based AgNPs as a natural cytostatic agent against oral squamous carcinoma. Utilizing nature’s resources and nanoscale science, they hold promise for enhancing oral cancer treatment outcomes and survival rates.

Over 422 million people worldwide suffer from diabetes, causing 1.5 million fatalities annually. The existing medications have shortcomings, including poor glucose control and adverse effects. The present study aimed to create possible alpha-glucosidase inhibitors utilizing a curculigoside A derivative ligand-based model.

A pharmacophore model was constructed utilizing the structure information of curculigoside A derivatives and PharmaGist. Subsequently, virtual screening, molecular docking, and molecular dynamics were employed to simulate the hits.

From six training sets, eleven pharmacophore models were developed; the model with the highest score (18.0435) was chosen for further analysis. Using the verified pharmacophore model, 270 547 chemicals from the ZINC natural product database were subjected to virtual screening. Subsequently, molecular docking was performed on the top 1000 hits with AutoDock Wizard from PyRx. This analysis unveiled 434 hits with better binding energies than acarbose, the native ligand. Subsequently, second optimal docking configurations were evaluated with AutoDock 2.4; this process yielded the discovery of three prospective inhibitors (ZINC000150350051, ZINC000008382292, and ZINC000085595291) characterized by the most advantageous binding energies. To evaluate the stability and dynamics of these ligand-receptor complexes, Gromacs 2022 molecular dynamics simulations were executed for one hundred nanoseconds. Out of the three hits, ZINC000085595291 (Hit03) exhibited good energy components and interaction stability constantly during the simulation.

The integrated computational strategy identified promising alpha-glucosidase inhibitors in curculigoside A compounds, highlighting the potential of ZINC000085595291 (Hit03) as a potential diabetes therapeutic agent.

Healthcare-associated infections are a global public health issue with farreaching individual and economic repercussions. The microorganism’s multi-resistance frequently increases the risk that can be lowered by using biomolecules of medicinal plant essential oils (EOs). This study investigated the phytochemical components and antimicrobial potential of the EOs of Moroccan Origanum compactum and Ruta montana gathered from Taza Region.

The EOs’ chemical analysis was performed by GC/MS and their antimicrobial effects were assessed by the microplate dilution method against eight nosocomial resistantbacterial strains.

The main constituents of O. compactum EO were Thymol (29.56%), carvacrol (26.44%), γ-terpinene (18.86%) and p-cymene (12.01%), while those of R. montana EO were 2-undecanone (85.76%), 2-nonanone (3.95%), 2-decanone (3.67%) and 2-dodecanone (1.94%). The O. compactum EO had important antimicrobial effects on all bacteria experienced. The lower minimum inhibitory concentration (MIC) values were obtained for the tested Staphylococcus species (0.062%, 0.125% (v/v)) while the highest one (2% (v/v)) was obtained for Klebsiella pneumonia and Pantoea spp. The R. montana EO showed MIC values of 4% (v/v) for Pantoea spp. and 8% (v/v) for the other tested strains except K. pneumonia for which no effect was shown.

Therefore, these EOs, especially the O. compactum one, have an interesting antibacterial potential against nosocomial infections and might be used to develop new antimicrobial agents.

The liver and kidney are the main sites of aluminum (Al) accumulation. Lifetime exposure to significant amounts of Al is inevitable, hence its toxicity on the liver and kidney should be a health concern. Natural antioxidants have been proven to alleviate pathologies in various liver and kidney injuries. However, the effect of olive leaf extract (OLE) on Al-exposed animals is yet to be confirmed. This study aimed to investigate the OLE effect against AlCl3 chronic exposure in rats’ liver and kidneys.

Thirty-two male Wistar rats were divided into four groups (n=8), including the control group, the AlCl3 group treated with 128 mg/kg AlCl3 solution, as well as AlCl3 +OLE50, and AlCl3 +OLE100 groups (Other than AlCl3 they received 50 and 100 mg/kg of OLE, respectively, 2 hours after AlCl3 administration). All treatments were given orally for 12 weeks. All groups were evaluated for liver and kidney histopathological features, then scoring was performed.

AlCl3 administrations produced histopathological lesions in the liver and kidney, indicated by increased liver necro-inflammatory grades, ballooning scores, and renal inflammatory cell infiltration (P<0.05). OLE100 mg/kg significantly reduced liver necroinflammatory grade, ballooning score, and kidney inflammatory cell infiltrations. The dose of 50 mg/kg also reduced these parameters (P<0.05), except for the liver necro-inflammatory grade. There was a significant correlation between OLE dose and liver necro-inflammatory grade and ballooning score amelioration.

OLE ameliorates liver and kidney histopathological features induced by oral Al chronic exposure in a dose-dependent manner.