Journal of Herbmed Pharmacology
Volume:12 Issue: 2, Apr 2023

This overview on Volkameria inermis (Lamiaceae) is the first in updating information on the chemical constituents and pharmacological properties of the species, notably on its unique ability in ameliorating motor tics. The information was procured from Google, Google Scholar, PubMed, PubMed Central, Science Direct, J-Stage, and PubChem. Previously named Clerodendrum inerme (Verbenaceae), V. inermis is a scrambling or scandent coastal shrub in the tropics and sub-tropics. From different parts of the plant, compounds such as flavonoids, diterpenes/diterpenoids, sterols, triterpenes/triterpenoids, iridoid glycosides, phenolic glycosides, phenylethanoid glycosides (PEGs), phenylpropanoid glycosides (PPGs), chalcones, and sesquiterpenes have been reported. Major pharmacological properties of V. inermis include anti-cancer, anti-inflammatory, antioxidant, hepatoprotective, analgesic, and antibacterial activities. Other properties include anti-tyrosinase, antifungal, neuroprotective, hypotensive, hypoglycemic, amyloid-β aggregation, wound healing, antipyretic, and larvicidal activities. A unique pharmacological property of V. inermis leaf extract, discovered by scientists from Taiwan, is the amelioration of motor tic disorders, a spectrum of Tourette syndrome. This property included a case report, three in vivo studies, and one patent. Areas of further research of V. inermis are suggested.

Cardiotoxicity is one of the main complications of chemotherapy that increases morbidity and mortality in cancerous patients. The present systematic review aimed to investigate the protective effects of berberine (Ber) on doxorubicin (Dox)-induced cardiotoxicity. The study protocol was developed following the PRISMA statement. An extensive search was performed in multiple databases, including Embase, PubMed, Cochrane library, Web of Science, and Scopus. After defining the inclusion/exclusion criteria of the study, 12 records were included. The desired data of the retrieved articles were extracted from the studies and imported into an Excel form and ultimately, the effects, probable outcomes and mechanisms were surveyed. By activating sirtuin 1 (SIRT1), Ber caused reduced oxidative damage and loss of mitochondria integrity in cardiomyocytes. It also regulated autophagy and apoptosis via down-regulating AMP-activated protein kinase (AMPK), nucleotide-binding oligomerization domain, leucine rich repeat, and pyrin domain containing protein (NLRP) activation. Moreover, Ber increased superoxide dismutase (SOD), catalase (CAT), and plasma glutathione peroxidase (GSH-Px) activities, reduced the levels of malondialdehyde (MDA), up-regulated SIRT3, and subsequently reduced oxidative stress in cardiomyocytes and loss of mitochondria integrity, leading to developed apoptosis and regulating the histopathological and electrocardiogram changes in the myocardium. It also ameliorated the DOX-induced calcium ions (Ca2+) and iron overload. Ber reduced oxidant and inflammatory activity, and regulated apoptosis of cardiomyocytes, thus protecting the cells against DOX-induced cardiotoxicity.

The current healthcare system is insufficient to deal with the global impact of rising diabetes, necessitating the development of better alternatives, such as plant-derived natural compounds, to improve glucose tolerance. Therefore, the present study evaluated the phytoconstituents of the aqueous leaf and rhizome extracts of an unnoticed plant species, Kaempferia pulchra. In addition, the in vitro anti-hyperglycemic efficacy and antioxidant activities of the derived terpenoid fraction from the plant extracts were also assessed.

The aqueous extracts of K. pulchra leaves and rhizomes were screened for phytoconstituents using gas chromatography-mass spectrometry. Colorimetric techniques were used to determine the terpenoid fraction’s total phenolic and flavonoid content. Terpenoids’ in vitro antioxidant properties were examined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA) and ferric reducing power assay, proceeded by α-amylase and α-glucosidase inhibition tests, and anti-hyperglycemic potential was determined utilizing the terpenoid’s fraction.

The preliminary phytochemical analysis revealed that the terpenoids obtained from the leaf had the highest total phenol and flavonoid content. Both leaf and rhizome extracts had modest antioxidant capacities compared to ascorbic acid. Similarly, the rhizome extract had significantly higher α-amylase inhibitory activity than the standard acarbose (P < 0.05). Overall, the rhizome extract of K. pulchra outperformed the leaf extract in terms of antioxidant and antidiabetic potential.

Kaempferia pulchra is a natural source of terpenoids with several therapeutic qualities, especially for managing diabetes. However, further research is needed to validate some of the claims ascribed to this plant.

Liver tissue malfunction is a severe worldwide health concern that arises from various chronic liver conditions. The goal of this investigation was to look into the anti-fibrotic effect of apigenin (APG), an antioxidant found in various plants, versus thioacetamide (TAA)-triggered hepatic scarring in rats and the potential mechanisms behind it.

TAA was administered thrice weekly (100 mg/kg, i.p.) for two weeks to produce hepatic scarring. APG was administered after TAA for 14 days (5 or 10 mg/kg, orally). Thereafter, hepatic liver enzymes, inflammatory markers, fibrotic indicators, and histopathological changes were evaluated.

TAA increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced albumin and total protein, elevated hepatic level of lipid peroxidation, focal adhesion kinase (FAK), hypoxia-inducible factor-1α (HIF-1α), and inflammatory cytokines, decreased interleukin-10 (IL-10), reduced hepatic expression of peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and elevated serine-threonine protein kinase (AKT) expression. Furthermore, TAA increased hepatic contents of collagen I, connective tissue growth factor (CTGF), hydroxyproline, and alpha-smooth muscle actin. On the other hand, APG evaded these changes and mitigated the harmful effects of TAA in a dose-dependent way. Histopathological and immunohistochemical observations reinforced these biochemical outcomes.

APG can potentially alleviate liver fibrosis mediated via FAK and HIF1 inhibiting signaling pathways.

Cassia fistula Linn. (CF) is a well-known Thai medicinal plant and a source of many bioactive compounds. The present work designed to examine the anticancer effects of pod shell and leaf of CF extracts on a human breast cancer cell line via the suppression of tumor development and metastasis. The expression of an epidermal growth factor receptor (EGFR) expression was interested to explore.

The in vitro anticancer activities of the CF pod shell and leaf extracts, including cell cytotoxicity, cell growth, cell migration, cell death, and reactive oxygen species (ROS) formation were evaluated using sulforhodamine B (SRB), colony forming, wound healing, and flow cytometric analysis, respectively. The EGFR protein expression was determined by western blot analysis, which is related to increased cancer cell growth and resistance to apoptosis.

CF pod shell and leaf extracts showed significant toxicities against MCF-7 cells and inhibited the cancer cells proliferation and migratory ability of breast cancer MCF-7 cells in concentration- and time-dependent manners. Both extracts induced late cell apoptosis and significantly generated ROS formation at a dose of 250 mg/mL. Western blotting data exhibited low levels of EGFR protein expression after treating with the extracts at a dose of 1000 mg/mL.

CF pod shell and leaf extracts are able to reduce breast cancer cell proliferation, increase cell apoptosis, and suppress cell migration through the downregulation of EGFR expression indicating anticancer activities.

Tooth decay as the most common infectious-nutritional disease in the world. The current work aims to investigate the antibacterial effect of thymol-loaded chitosan nanocomposite (TLCN) against Streptococcus mutans and Actinomyces viscosus as the main cariogenic bacteria.

Antibacterial activity of TLCN was assessed on S. mutans and A. viscosus. The effects on protein leakage in the tested bacteria, as well as its cytotoxicity, were studied by Bradford’s method and cell viability assay, respectively.

The size of the nanocomposite varied from 100 to 600 nm. The best minimum inhibitory concentration (MIC) related to nanocomposite + chlorhexidine was reported 2.66 for both bacteria. TLCN dose-dependently increased the protein leakage (P < 0.05). The 50% cytotoxic concentration (CC50) of nanocomposite against on normal (HGF1-PI1) and cancer (KB) cells were 149.6 and 68.4 μg/mL, respectively.

TLCN, especially in combination with chlorhexidine, displayed potent antibacterial effects against the main cariogenic bacterial causes. Nevertheless, other examinations are required to illuminate the precise mechanisms and its toxicity mainly in clinical settings.

Candidiasis therapy is a complicated concern because of the occurrence of resistance to antifungal agents. We studied the anti-fungal effects of Ferula macrecolea essential oil (FME) against Candida albicans resistant and sensitive strains, as well as its cytotoxic effects against normal and cancer cell lines.

The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of F. macrecolea essential oil against C. albicans ATCC 5027 and C. albicans ATCC 76616 were studied by broth-microdilution approach. The cytotoxicities of FME on HGF1-PI (normal gingival cell line) and HepG2 (liver cancer cell line) cells were also studied.

The main components of essential oil were terpinolene (71.25%), n-nonanal (6.32%), and linalool (3.95%), respectively. The MIC and MFC of FME on C. albicans sensitive to nystatin were 1.6 and 2.0 μg/mL, respectively. The MIC and MFC of FME on nystatin-resistant strains were 3.3 and 4 μg/mL, respectively. The MIC and MFC of terpinolene on C. albicans sensitive to nystatin were 0.8 and 1.0 μg/mL, respectively. The MIC and MFC of terpinolene on nystatin-resistant strains were 2 and 2.4 μg/mL, respectively. The essential oil and terpinolene had no significant cytotoxic effects against normal cells.

We revealed the promising antifungal effect of F. macrecolea essential oil and its main component, terpinolene, against C. albicans sensitive and resistant to nystatin with no significant toxicity on normal cells.

Ovariectomies rats were used to assess the preventive effects of almond and primrose oils on their lipid and neurochemical profiles.

The experimental groups were as follows: Group 1: A negative control group. Group 2: Rats given an oral dose of almond oil (800 mg/kg/d) for 30 days. Group 3: Rats given an oral dose of primrose oil (500 mg/kg/d) for 30 days. Group 4: Untreated ovariectomized rats. Group 5: Ovariectomized rats given an oral dose of almond oil (800 mg/kg/d) for 30 days. Group 6: Ovariectomized rats given an oral dose (500 mg/kg/d) of primrose oil daily for 30 days.

Oral administration of almond and primrose oils significantly decreased mean (P < 0.05) serum total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), and very low-density lipoprotein cholesterol (VLDL-C) concentrations and raised high-density lipoprotein cholesterol (HDL-C) in the ovariectomized groups compared to group 4 (P < 0.05). They also increased leptin and estradiol (E2) concentrations in groups 5 and 6. Administration of oils showed a marked increase in noradrenalin, dopamine, and 5-hydroxytyramin levels and a marked decrease in PGE2 and COX-2 levels (P < 0.05). Rats given almond and primrose oils revealed minor capillary congestion in the hippocampus in brain sections.

Administration of almond or primrose oils may improve central nervous system functions and decrease the risk of cardiovascular illnesses. They also might be effective against atherosclerosis, inflammation, endocrine disorders, and cognitive impairments for women who undergo surgical menopause prior to their natural menopause.

Multidrug resistance (MDR) is primarily associated with reduced intracellular drug accumulation owing to overexpression of p-glycoprotein, an active efflux transporter. Competitive inhibition or allosteric modulation of p-glycoprotein may alter the pharmacokinetics of the drugs that serve as substrates, resulting in enhanced drug bioavailability and tissue penetration. This study endeavors to assess the efficacy of the components of reno-protective herbs in the inhibition of p-glycoprotein activity thereby enhancing the possibility of the retention of co-administered renal medications inside the target cells.

Drug-likeness and pharmacokinetic properties were determined to ensure the safety and efficacy of herbal constituents. Molecular docking employing the CDOCKER module of Discovery Studio was performed to investigate the binding affinity between the active constituents and the p-glycoprotein receptor (6C0V). Molecular dynamics simulation was utilized to further assess the stability of the complex of receptors with the component bearing its maximal affinity.

The analyses suggested that the inhibitors viz., atisine, kutkin, and embelin from Aconitum heterophyllum, phylloquinone from Calendula officinalis, stigmasterol from Paederia foetida, and convallamarogenin from Convallaria majalis demonstrated maximum binding affinity towards p-glycoprotein.

Atisine may thus be identified as the lead compound in the augmentation of drug bioavailability inside the cell, along with its reno-protective efficacy.

Antioxidant and hypoglycemic properties of some plant seeds are considered natural preventives for diabetic-associated glycation. This study is concerned with the evaluation of the bioactive components of black chia and garden cress seeds and the examination of their modulatory effects on hyperglycemia and associated glycation induced by streptozotocin (STZ) injection.

Forty male rats were divided into 4 groups, 10 rats each: Group 1 (healthy control group); group 2 (diabetic group): rats injected STZ intraperitoneally to induce hyperglycemia; group 3 and group 4: rats treated (after diabetic induction) with 1 mL (20% w/w) black chia and garden cress seed extract, respectively.

STZ injection caused marked hyperglycemia, oxidative stress, glycation, and inflammation condition with disturbance in organs functions and structural alterations in pancreatic tissue, while; treatment with black chia and garden cress seed extracts showed remarkable (P < 0.05) modulatory effects on hyperglycemia and associated disorders.

Black chia and garden cress seeds might be used in the management of diabetes and associated glycation.

Triphala, consisting of three fruits, Phyllanthus emblica L. (Phyllanthaceae), Terminalia bellirica (Gaertn.) Roxb. (Combretaceae), and T. chebula Retz, is a well-recognized Ayurvedic herbal formulation, used for various therapeutic purposes, including the treatment of dyslipidemia. Inhibitory activity against 3‑hydroxy‑3‑methylglutaryl‑coenzyme A (HMG‑CoA) reductase, a rate-limiting enzyme in the endogenous cholesterol synthesis pathway, is an essential target for the management of hypercholesterolemia. This in silico study aimed to investigate the HMG-CoA reductase inhibitory activity of the phytochemical compounds derived from Triphala formulation by employing molecular docking analysis.

Ten phytochemical constituents of Triphala formulation were selectively used for docking study by using the HMG-CoA reductase template (PDB: 1HWK). Docking analysis was performed using AutoDock 4.2. The candidates were ranked by the binding energy parameters.

From the docking studies, the phytochemical compounds with HMG-CoA reductase inhibition could be classified into 4 groups, including phytosterols, polyphenols, tannins, and flavonoids. Beta-sitosterol exhibited the highest binding affinity to HMG-CoA reductase with a binding energy of -7.75 kcal/mol.

These 10 phytochemical compounds in Triphala potentially exert their cholesterol-lowering effects via inhibition against HMG-CoA reductase. Nonetheless, further in vitro and in vivo experiments should be conducted subsequently to confirm this finding.

In Thailand, garlic and turmeric have been used widely as basic spices in Thai food and traditional medicine. Previous studies reported that both of them had antibacterial activities. A few data have shown that extracts from both herbs are type 3 secretion system (T3SS) inhibitors. Therefore, this study aimed to investigate anti-T3SS in garlic and turmeric extracts and identify their specific mechanisms.

Salmonella Typhimurium containing chromosomally infusion between the gene encoding SipA effector protein and strep-tag epitope was used for the determination of anti-T3SS in garlic and turmeric extracts. The mechanism of inhibition was identified by the determination of mRNA expression of T3SS genes with semiquantitative RT-PCR.

Garlic and turmeric extracts contained T3SS inhibitory activity at the concentrations of 100 μg/mL and 75 μg/mL, respectively. These extracts reduced the ability of bacterial invasion into epithelial cell cultures. However, the effective dose of both extracts did not affect bacterial growth or toxic effects on HeLa cells. Moreover, the results from RNA transcriptional levels illustrated that these extracts suppressed the transcription of the T3SS regulation genes.

It may conclude that garlic and turmeric extracts blocked T3S activity for the secretion of effector proteins and bacterial invasion by interfering the expression of the T3SS regulatory cascade. Therefore, the extracts from garlic and turmeric might be potential sources for the development of new anti-T3SS therapeutic agents.

Studies have shown that synthetic agents are connected with some complications. This work was designed to study the effects of vitamin C and Citrus sinensis fruit extract (CSFE) on viability, DNA synthesis, and apoptosis stimulation in human lung cancer cells (COR-L105).

The total contents of the phenolics, flavonoids, and ascorbic acid in CSFE were assessed through the Folin-Ciocalteu, aluminum chloride, and dinitrophenyl hydrazine methods, respectively. The cytotoxicity of vitamin C and CSFE on COR-L105 cells was evaluated by the cell viability assay. Measurement of the DNA synthesis was done through the BrdU solution assay. The expression levels of some apoptosis regulatory genes were also evaluated.

The total phenolic, flavonoids, and ascorbic acid contents of CSFE were 94.31 ± 2.27 gallic acid equivalents (mg/g) of dry extract, 63.26 ± 2.86 quercetin equivalents (mg/g) of dry extract, and 59 mg/L, respectively. The 50% cytotoxicity concentration (CC50) values of vitamin C and CSFE on cancer cells were 54.6 and 82.7.6 μg/mL, respectively. Vitamin C and CSFE dose-dependently declined the amount of DNA production in the cancer cells. The expression levels of caspase-3 and Bax genes were markedly (P < 0.001) elevated by vitamin C and CSFE, while they reduced the level of Bcl-2 gene (P < 0.05).

The findings showed the potent anticancer effects of vitamin C and CSFE against human lung cancer cell lines. DNA synthesis reduction and apoptosis induction can be considered as possible mechanisms of action. However, further surveys are necessary to clarify the accurate mechanism and their efficacy.

Garlic (Allium sativum) is widely used as a flavor-enhancing dietary ingredient and exhibits a wide spectrum of pharmacological effects. This study aimed to investigate the therapeutic effects of aqueous garlic extract to explore the bioactivity against 15-lipoxygenase (15-LOX) mediated inflammopathies.

In this study, the antioxidant (DPPH free radical scavenging assay and reducing power assay), anti-inflammatory (hypotonicity-induced hemolysis assay and 15-LOX inhibition assay) and anticoagulation (serine protease inhibition assay and prothrombin time assay) effects of the aqueous garlic extract were investigated. Furthermore, in silico molecular docking and dynamic simulation analysis of reported small compounds of garlic against 15-LOX1 and 15-LOX2 were performed to figure out the most efficient phytochemical ligands and validate the anti-inflammatory potential.

The DPPH scavenging effect and the reducing power of the extract were found with the IC50 of 213.87 ± 1.49 μgmL-1 and EC50 of 124.78 ± 3.39 μgmL-1, respectively. In the hypotonicity-induced hemolysis and 15-LOX inhibition assay, the IC50 values were observed as 147.59 ± 2.98 μgmL-1 and 250.05 ± 8.48 μgmL-1, respectively. The extract inhibited serine protease activity with an IC50 of 301.33 ± 1.31 μgmL-1 and prevented blood coagulation for 10.05 ± 0.35 minutes in prothrombin time assay. The in silico study identified Rhamnetin as a potential 15-LOX1 and 15-LOX2 inhibitor, and it exhibited a stable interaction with the targets throughout the 100 ns dynamic simulation.

The findings of this study provide molecular insights into garlic’s medicinal properties as well as its bioactive compounds, which can be potential therapeutic interventions for 15-LOX mediated inflammations.

Radiofrequency electromagnetic radiation (RF-EMR) from mobile phones was reported to cause neurological damage. Hispolon pyrazole (HP) and hispolon monomethyl ether pyrazole (HMEP) were tested for their RF-EMR protection in rats.

Juvenile Wistar albino rats were exposed to the mobile phone generating 2400 MHz radiation with a maximum power output of 2 W/kg (Specific absorption rate 1.6 W/kg) for 90 days at a rate of 2 hours/day, treated with HP and HMEP at 20 and 40 mg/kg body weight. The elevated plus maze (EMT) test was used for anxiety and exploration evaluation, the forced swim test (FST) for depression, the Morris water maze test and Y-maze test for learning and memory. The oxidative stress markers like glutathione, superoxide dismutase (SOD), catalase (CAT), and malonaldehyde (MDA), and the neurotransmitters such as gamma-aminobutyric acid, glutamate, dopamine, and acetylcholinesterase along with histopathology in the cortex, striatum, and hippocampus were evaluated to establish the mechanism of the neuronal alterations of HP and HMEP against RF-EMR-induced damage.

In the current investigation, HP at a higher dose of 40 mg/kg and HMEP at both doses significantly reduced the oxidative stress generated by RF-EMR from mobile phones and altered neurobehavioral, neurotransmitter, and histological alterations.

Based on the findings, HP and HMEP at a dose of 40 mg/kg are protective agents against long-term, continuous mobile phone use and can be regarded viable therapeutic agents.

Conventional medicines for Alzheimer’s disease (AD) have little efficacy and are linked to several severe effects, necessitating alternative therapy. The current study investigated the memory-enhancing effects and antioxidant activities of stem bark and leaf MeOH extracts of Prunus africana in scopolamine-induced amnesic mice. Several inclusions build up in brain tissue during AD progression and the brain clears them oxidatively. This makes the antioxidant activity a vital requirement for plant extracts that are used with great success to manage AD.

In this study, for each plant extract, thirty Swiss albino mice were randomly assigned to six groups; extract-treated, reference drug control, normal control, and negative control groups. The mice were then subjected to the Morris water maze task for four consecutive days, euthanized and their whole brains were assessed for antioxidant activities.

The studied extracts significantly (P < 0.01) reduced escape latencies of experimental mice in a dose-related manner, depicting their considerable memory-enhancing effects. The extracts also displayed significant (P < 0.01) enzymatic and non-enzymatic antioxidant activities.

The leaf and stem bark MeOH extracts of P. africana possess phytocompounds with spatial memory-enhancing effects and antioxidant activities.

The present work aimed to assess the anti-parasitic effects of limonene (LMN) against Giardia lamblia trophozoites and cysts.

Anti-Giardia activities of LMN (25, 50, and 100 μg/mL) were assessed against G. lamblia cysts and trophozoites for 15-360 minutes. The effects of LMN on the apoptosis stimulation G. lamblia parasites were determined by colorimetric protease assay.

Giardia trophozoites were more sensitive to LMN than cysts. The best effect of LMN was seen at 100 μg/mL. LMN markedly triggered caspase-3 activity by 10.2%, 25.3%, and 36.1%, respectively (P < 0.001).

We found the potent in vitro anti-giardia activity of LMN against G. lamblia parasites with the maximum activity at 50 and 100 μg/mL. However, additional surveys are necessary to reveal the specific efficacy, mechanisms, and safety of LMN.