Journal of Herbmed Pharmacology
Volume:11 Issue: 4, Oct 2022

Hibiscus sabdariffa L., belonging to the Malvaceae family, has been long used as herbal medicine, food, beverage, flavouring, and colouring agents. This study aims to review and document the evidence regarding the potential use of H. sabdariffa as ethnomedicine in some countries and its bioactive constituents and therapeutic properties. The electronic databases were used to search for the relevant information to the aims of this review up to March 2022. The high usage of H. sabdariffa as traditional medicine is due to its easy accessibility and low price. The plant is often used to treat intestinal problems, stomach disorders, and blood or liver toxicities. The plant contains phenolic compounds, including anthocyanins, flavonoids, and phenolic acids. The in vivo, in vitro, and clinical studies provide evidence that H. sabdariffa possesses therapeutic effects such as antihypertensive, antihyperlipidemic, antioxidants, antimicrobial, and antitumor activities. The studies provided scientific evidence for the statement of H. sabdariffa and its bioactive constituents in treating various diseases.

Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) constitutes a source of great concern to health authorities worldwide. Herbal medicinal products are used as a significant treatment option for highly active antiretroviral therapies, the efficacies of which are negatively impacted by the emergence of multidrug-resistant strains to the recommended treatment guidelines. This review provides an updated synopsis of available documents on herbal medicinal products with anti-HIV activities. Concurrent consumption of herbal products with conventional drugs, which is often necessitated by co-morbidity of HIV with other diseases, can potentially alter the pharmacokinetics of the co-administered orthodox drugs. Phytochemical constituents of the herbal medicinal products with antiretroviral activities were identified, and their potential to mediate pharmacokinetic changes through modulation of drug-metabolizing enzymes and P-glycoprotein was reported. Herb-drug interactions (HDIs) that can result in significant adverse effects were also discussed with documenting the information for the therapeutic utility of these clinically effective antiretroviral herbal medicinal products with potential for development into newer anti-HIV drugs.

Triphala is a medicinal plant that can improve anthropometric parameters. Although Triphala is widely used, especially in India and Thailand, its efficacy is still controversial. Consequently, the purpose of this meta-analysis and meta-regression analysis was to assess the safety of Triphala and its effects on anthropometric parameters. A comprehensive review and meta-analysis of randomized controlled trials assessing the safety of Triphala and its effects on anthropometric parameters were conducted by searching PubMed, ScienceDirect, Web of Science, and ThaiLIS databases. Two authors independently conducted the study selection and data extraction and evaluated the quality of the studies. The clinical therapeutic effects and adverse events of Triphala were evaluated and aggregated using a random-effects model. The chi-square and I2 tests were used to assess heterogeneity between the studies. Seven trials with a total of 458 patients were included. The Triphala-treated groups demonstrated a considerable decrease in body weight (BW) (weighted mean difference [WMD]: −2.99 kg; 95% CI: −5.31, −0.67; P = 0.012; I2 = 94.4%), body mass index (BMI) (WMD: −0.79 kg/m2; 95% CI: −1.52, −0.07; P = 0.032; I2 = 90.4%), and waist circumference (WC) (WMD: −1.86 cm; 95% CI: −3.10, −0.62; P = 0.003; I2 = 88.8%). During the treatment period, there were no reports of serious adverse events related to Triphala. However, there was no association between the dose or duration of treatment and any of the recorded outcomes. This meta-analysis revealed that Triphala significantly improved BW, BMI, and WC. Nevertheless, substantial, well-designed randomized controlled studies are necessary to confirm this finding.

Ficus capensis has been used in traditional medicine to treat anaemia, tuberculosis, convulsion, pains, wounds, respiratory disorders, and other health challenges. This study investigated the effect of F. capensis ethanolic leaf extract in phenylhydrazine (PHZ)-induced anaemia in Wistar rats.

Induction of anaemia was done by intraperitoneal administration of PHZ (40 mg/kg for 48 hours). A normal group and an anaemic group were treated daily with a single dose of 20 mL/kg of distilled water and considered as control and anaemic (non-treated) groups. Then, the remaining groups were treated with 100, 200, and 400 mg/kg of ethanol extract of F. capensis leaves for 21 days, respectively. Blood samples from the rats were run in three batches of baseline, post anaemia induction, and post-treatment. Phytochemical screening and acute toxicity tests of the extract were also carried out following standard procedures.

The results showed a consistent significant increase in haematological parameters among various experimental groups. Haemoglobin (Hb), red blood cell (RBC) count, mean corpuscular volume (MCV), packed cell volume (PCV), mean cell haemoglobin (MCH) and Mean cell haemoglobin concentration (MCHC) values of treated rats were significantly increased compared to the anaemic control. The secondary metabolites of leaf extract were alkaloids, saponins, tannins, steroids, flavonoids, phenols, and reducing sugar, while the acute toxicity test was found to be non-toxic at 5000 mg/kg in rats.

The ethanol leaf extract of F. capensis might provide an alternative cure for anaemia and boosts blood count.

Aucoumea klaineana, Canarium schweinfurthii, Cymbopogon nardus, Dacryodes edulis, and Eucalyptus citriodora are of Gabonese origin, believed to have insecticidal activity. This study contributes to vector control by the insecticidal activities (larvicidal and ovicidal) of five essential oils from these plants against Anopheles gambiae, a major vector of malaria in Gabon.

The essential oils were extracted by hydrodistillation. Larvicidal and ovicidal effects of essential oils were performed using different concentrations on third and fourth instar larvae and eggs of A. gambiae vectors. The effects of these oils were examined on the mortality rate of larvae and eggs.

The essential oils of A. klaineana, C. schweinfurthii, C. nardus, A. edulis, and E. citriodora showed greater activity against mosquito larvae (7.33 < LC50 < 107.14) compared to eggs (22.80 < LC50 < 64.63). D. edulis showed the highest activity against Anopheles gambiae eggs and larvae. Of all plants, essential oils from A. klaineana showed the lowest activity of A. gambiae eggs and larvae. Larvae were more sensitive than eggs. All essential oils were toxic to the various aquatic vectors of malaria.

The study reveals the potential ovicidal efficacy and larvicidal activity of these plants against A. gambiae.

Non-alcoholic steatohepatitis (NASH) is considered as current and critical liver disease and liver fibrosis is an initial step to vast NASH injuries. Allantoin is an important and sure composite, which has remark effects on inflammation and apoptosis. This study was done to evaluate the allantoin duty on liver fibrosis and its pathways in mice-induced NASH.

In the control groups, inbred mice took saline and allantoin. In the NASH group, NASH was provided with a methionine-choline deficient (MCD) diet for eight weeks, and finally, in the NASH-Alla group, allantoin was injected for four weeks in the mice with an MCD diet. For collagen deposition evaluation, trichrome Masson staining and for cellular evaluations, real-time PCR and ELISA assays were performed.

Allantoin treatment improved liver steatosis and fibrosis. Protein expression of nuclear factor kappa B (NFĸB-p65) (P < 0.05) and genes expressions of transforming growth factor-β (TGFβ) (P < 0.001), cyclooxygenase 2 (COX2) (P < 0.001), matrix metalloproteinases 9 (MMP9) (P < 0.001) and alpha-smooth muscle actin (αSMA) (P < 0.001) were also decreased. Moreover, hepatic prostaglandin E2 (PGE2) levels lowered after allantoin treatment (P < 0.05).

Attenuating effects of allantoin on liver fibrosis may be due to the inhibition of NFĸB/TGFβ, NFĸB/MMP9, and NFĸB/Cox2/PGE2 pathways, which decrease αSMA expression and collagen deposition and ameliorate liver fibrosis.

Anemia is a common health condition caused by a decrease in red blood cells. Some medicinal plants are used as a remedy to treat anemia. This study compares the anti-anemic properties of different doses of the aqueous extracts of Ficus capensis (AEFC) and its combination with the aqueous extract of Cnidoscolus aconitifolius (AECA) in phenylhydrazine-induced anemic rats.

Anemia was induced by intraperitoneal injection of 20 mg/kg phenylhydrazine for five consecutive days. Graded doses of the extracts were given by oral gavage once a day continuously for 30 days. At the end of the treatment, blood was collected for hematological analysis.

The antianemic effects of AEFC and its combination with AECA were demonstrated by significant increases (P < 0.05) in the hemoglobin (HGB), packed cell volume (PCV) and red blood cell (RBC) count of the extract-treated groups compared to the anemic control group. There was a better increase in the HGB levels of a combination of 400 mg/kg AEFC + AECA (13.97 ± 2.53) compared to 400 mg/kg AEFC (12.06 ± 0.02). The PCV increased more in 400 mg/kg combination of AEFC + AECA (41.94 ± 0.37) compared to 400 mg/kg AEFC (36.31 ± 1.51). A significant (P < 0.05) increase was observed in the RBC count of a combination of 400 mg/kg AEFC + AECA (6.36±0.51) compared to 400 mg/kg AEFC (4.75 ± 0.46).

Although AEFC improved the haematological parameters of the animals when administered alone, its combination with AECA yielded a far much better result by totally restoring the haematological parameters of the phenylhydrazine-induced anemic rats to normal.

α-Glucosidase is the major enzyme implicated in intestinal glucose absorption, and its inhibition is a target for the management of diabetes mellitus. This study investigated the in vitro α-glucosidase inhibitory activity of extracts from different parts of 20 selected medicinal plants and the potential for plant-part substitution and plant species combinations used by traditional healers to treat diabetes.

Acetone and petroleum ether extracts from different parts of 20 plant species traditionally used to treat diabetes were individually evaluated in vitro using an α-glucosidase assay. The potential for plant-part substitution was investigated by including leaf extracts where non-renewable parts are used traditionally. The extracts of plant species were combined and investigated as used traditionally.

Anthocleista grandiflora stem bark acetone, Artabotrys brachypetalus leaf petroleum ether, and Dichrostachys cinerea root petroleum ether extracts exhibited remarkable α-glucosidase inhibitory activities with IC50 values of 9, 14, and 12 μg/mL, respectively. The α-glucosidase inhibitory activities of A. grandiflora, A. brachypetalus, Asparagus virgatus, Brackenridgea zanguebarica, Maerua edulis, Pterocarpus angolensis, and Tabernaemontana elegans were documented for the first time, suggesting their antidiabetic potential. The leaf acetone extracts of Brackenridgea zanguebarica and Terminalia sericea had similar α-glucosidase inhibitory activities when compared to their stem bark and root, respectively. The combination of Dichrostachys cinerea leaf with Elephantorrhiza elephantina root, extracted with petroleum ether, resulted in a synergistic inhibitory effect.

The valorization of these newly documented species holds potential for the discovery of more effective and perhaps novel antidiabetic remedies or drug principles.

Zaringiah (Dracocephalum kotschyi) is an Iranian endemic herbal plant naturally growing in the Isfahan and Khorasan provinces. Hydroalcoholic extract of Zaringiah has anti-inflammatory, antispasmodic, and immunomodulatory properties. So far, the effect of Zaringiah extract on contraction induced by histamine and serotonin (5-HT) has not been reported. The objective of this research was to investigate the antispasmodic effect of hydroalcoholic, aqueous, chloroform, and ethyl acetate extracts of Zaringiah on rabbit ileum smooth muscle contractions induced by histamine and 5-HT.

Khorasani variant of Zaringiah was used in this study. Aqueous extract was prepared by decoction, while hydroalcoholic extract was obtained by the maceration technique. Chloroform and ethyl acetate fractions were obtained using a solvent in solvent extraction technique. Rabbit isolated ileum was set up in an organ bath filled with Tyrode’s solution. The effects of the above extracts were examined on contractions induced by histamine or 5-HT and compared with each other.

Hydroalcoholic extract of Zaringiah inhibited the rabbit ileum contractions induced by histamine (IC50 = 76 ± 7.7 μg/mL) and 5-HT (IC50 = 60 ± 6.4 μg/mL), as well as spontaneous contractions (IC50 = 63 ± 15 μg/mL). The aqueous extract, as well as chloroform and ethyl acetate fractions, concentration-dependently inhibited spontaneous, histamine, and 5-HT induced contractions.

There was not a significant difference among the inhibitory actions of hydroalcoholic, aqueous, chloroform, and ethyl acetate extracts of Zaringiah on rabbit ileum, indicating the distribution of active constituents in both polar and non-polar mediums.

Sclerocarya birrea stem-bark is widely used for the treatment of many medical conditions. Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular complications of diabetes mellitus. The study, other than phytochemical composition, evaluated the anti-glycation and AGEs-protein cross-link breaking effects of S. birrea stem-bark extracts.

Different S. birrea extracts and aminoguanidine (used as control) were incubated with bovine serum albumin (BSA) and glucose/fructose at 37oC for 40 days. Amounts of fluorescent AGEs (FAGEs) and immunogenic AGEs formed were determined. Anti-glycation activity percentage of each extract and aminoguanidine was calculated. Their AGEs-protein cross-link breaking abilities were also assessed. Standard techniques were employed for phytochemical screening. Volatile compounds were identified by means of gas chromatography mass spectrometry (GC-MS).

S. birrea stem-bark n-hexane extract was statistically more effective than aminoguanidine against the formation of total immunogenic AGEs (P<0.05). For FAGEs, ethyl acetate, methanol, and water extracts exerted significantly higher anti-glycation effects than aminoguanidine (P<0.001). Methanol extract exhibited the highest anti-glycation effect with an average IC50 value of 0.142 mg/mL against FAGEs. All extracts were effective in releasing BSA from the preformed collagen-AGEs-BSA cross-links. GC-MS enabled the identification of many biologically important compounds, including campesterol, stigmasterol, and 1-heptatricontanol.

S. birrea stem-bark has a potential for usage in the management of complications in uncontrolled glucose metabolism.

This work aimed to determine the antifungal effects of zinc nanoparticles (ZnNPs) green synthesized by Lavandula angustifolia extract, alone and along with nystatin against Candida albicans.

ZnNPs were green synthesized with L. angustifolia extract by microwaves method. Antifungal effects of ZnNPs were studied by measuring the minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) using the broth microdilution method based on the modified M27-A3 protocol on yeasts, recommended by the Clinical and Laboratory Standards Institute (CLSI). Effects of green synthesized ZnNPs against human normal fibroblast-like Gingiva (HGF1-PI1) and human epithelial-like oral cancer (KB) cell lines were studied by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method.

The ZnNPs showed a spherical shape with some grains of different lengths. The best levels of MIC and MFC were connected to the combination of ZnNPs + nystatin with values of 0.204 and 0.250 μg/mL, respectively. The combination of ZnNPs with nystatin compared to the nystatin group had a significantly better antifungal effect on C. albicans (P < 0.001). The 50% cytotoxic concentrations of ZnNPs against normal (HGF1-PI1) and cancer (KB) cells were 172.3 and 83.2 μg/mL, respectively.

We found that ZnNPs plus nystatin had a potent antifungal effect against C. albicans. These findings indicated the cytotoxic effects of green synthesized ZnNPs on cancerous cells, whereas they were nontoxic for normal cells. Additional studies are necessary to explain the accurate mechanism and toxicity.

The first and most prevailing cells that glycyrrhizin (GL) and glycyrrhetinic acid (GA) encounter are red blood cells (RBCs). However, what follows this event is poorly understood. This study aims to evaluate the effect of GL and its derivatives on the integrity of human RBCs.

The integrity of human RBC was assessed under normal isotonic conditions and following osmotic and nystatin-induced colloid-osmotic stress by measuring the amount of hemoglobin released. The pore size was determined by the osmotic protection method.

GL was found to be virtually non-hemolytic. However, removal of the carbohydrate moiety of GL imparted significant RBC lytic activity to the cis-(beta-) but not to the trans-(alpha-) isoform of GA. The hemisuccinate radical at position C3 (carbenoxolone) greatly diminished the hemolytic property of GA. The RBC lysis occurred by colloid-osmotic mechanism due to the formation of hydrophilic pores with the radius of ~2.3 nm. At the sublytic doses, the two stereo-isoforms displayed opposite effects on the osmo-resistivity of human RBC: osmoprotection for alpha-GA and osmotic sensibilization for beta-GA. Similar osmotic sensibilization was also observed for GL and carbenoxolone. The two stereo-isoforms exhibited different but not opposite weakening effects on the resistivity of the RBC to the colloid-osmotic stress induced by nystatin, a pore-former. The weakening effect was found intermediate for GL and absent for carbenoxolone.

Upon intestinal digestion and absorption, depending on the structure and dosage, the GL hydrolysis products interact with RBC with both beneficial and detrimental consequences.

The production of large amounts of reactive oxygen species in severe malarial infection is due to parasite invasion to erythrocytes. Malaria resistance to medication has left malaria-endemic countries with no alternate source of medications but traditional medicine. One of such plants utilized by traditional healers is Phyllanthus amarus. Therefore, this study aims at ascertaining the antiplasmodial and cytotoxic activities of P. amarus and its specific actions on retaining erythrocyte viability and antioxidant activity.

Antiplasmodial and erythrocyte viability activities were determined in vitro via parasite suppression and tetrazolium-based colorimetric assays, respectively. Antioxidant capacity was determined by measuring extract’s ability to inhibit lipid peroxidation, scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide ions, reduce iron(III) ions, and chelate iron in vitro using documented methods.

Alkaloid extracts of P. amarus showed great antiplasmodial activity (IC50=0.52μg/mL) and low cytotoxic activity (CC50=54.95 μg/mL). Erythrocyte viability assay showed the minimal impact of the extract on the uninfected erythrocytes but improved viability of the infected RBC in a dose dependent manner, and antioxidant activity manifested mainly in its iron chelating activity (EC50=0.34 μg/mL).

This study suggests that the alkaloid extract of P. amarus has significant antiplasmodial and antioxidant activities. These activities promoted the repair of parasite-induced free radical damage to the erythrocyte membrane but distorted the parasites redox balance and defense mechanism, and hence survival rate as indicated by the parasite suppression associated with alkaloid extract treatment of malarial infection.

The current study aimed to investigate if insulin supplemented with phenolic fraction concentrates (PFC) improves chronic hyperglycemia-related behavioral changes by mitigating oxidative stress in diabetic rats exposed to chronic mild stress (CMS).

Experimental type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). After diabetes confirmation, rats were treated with insulin supplemented with PFC and exposed to two unpredictable mild stressors per day for 12 weeks. Body weight changes, fasting blood glucose (FBG), and corticosterone levels were evaluated. The behavioral tests were performed to evaluate anhedonia, anxiety, and depressive-like behaviors. Twenty-four hours after behavioral tests, all rats were anesthetized, and the blood was collected for the analysis of lipid, hepatic, and renal parameters. Finally, the brain areas (striatum, hippocampus, and prefrontal cortex), pancreas, and adrenal glands were dissected for the analysis of oxidative stress markers.

The results of this study revealed that treatment with insulin supplemented with PFC for 12 weeks significantly enhanced antioxidant defenses (catalase [CAT] and superoxide dismutase [SOD]) and reduced oxidative stress damage (nitric oxide and malondialdehyde [MDA]), especially in brain regions (prefrontal cortex, hippocampus, and striatum) in stressed diabetic rats (P < 0.001). This combination also ameliorated the corticosterone level (P < 0.001) as well as glucose homeostasis (P < 0.001) and lipid parameters (P < 0.001), which are markedly altered in T1D associated with stress.

The associated treatment possesses important anxiolytic and antidepressant-like effects in this rat model, which might be mainly mediated by its capacity to protect brain cells against reactive oxygen species (ROS) triggered by T1DM and/or chronic stress.

Diabetes mellitus is a common global cause of sudden unpredictable death if undiagnosed and untreated. Costus afer (Costaceae) is a tropical plant with quite a lot of pharmacological properties. This study investigated the prophylactic and antidiabetic properties of ethyl acetate fraction of C. afer in streptozotocin-induced diabetic rats.

Acute toxicity (LD50) test was done using Lorke’s method. Haematological indices were determined using haematology autoanalyser. The biochemical assays were done using standard diagnostic methods.

The lethal dose was 3807.9 mg/kg. There was a significant reduction (P < 0.05) in the fasting blood glucose concentration from week one to week four in the group that was pre-treated and later post-treated with 200 mg/kg body weight (bw) of the ethyl acetate fraction of C. afer leaves compared with the untreated diabetic control. The result of the hematological parameters revealed a significant increase (P < 0.05) in the hemoglobin, packed cell volume (PCV), and platelet count of the group pretreated and treated with 200 mg/kg of the fraction compared with the untreated diabetic control. The result of the biochemical assays revealed a far much better recovery from the disruptions caused by the induction of experimental diabetes as seen in the groups that were initially pretreated with 100 and 200 mg/kg before the induction of diabetes compared with the groups treated with the same dose but without pretreatment.

C. afer might be used for the prevention and management of diabetes mellitus. Its safety is evidenced by its effects on the hematological and biochemical indices.

Candida albicans is an important opportunistic pathogen that is responsible for most fungal infections in humans. Secondary metabolites are known to be antimicrobial and antifungal agents. This study aimed to investigate the chemical composition of Prangos ferulacea and P. uloptera essential oils and evaluate the sensitivity of four genera of Candida.

After collecting plant samples, their essential oils were extracted by the distillation method, and their components were analyzed using Gas chromatography–mass spectrometry to identify constituents. In total, 48 species of Candida isolated from clinical specimens were examined in this study. The antifungal activities of essential oils of P. ferulacea and P. uloptera were evaluated according to CLSI M27-A3 compared to fluconazole.

Out of the two tested plants, P. ferulacea had the lowest minimum inhibitory concentration (MIC) against Candida species. However, MIC of this plant against C. albicans isolates was higher than 0.121 μL/mL non-albicans species. Both plants were able to inhibit non- albicans species with MIC90 values of 0.0097 and 0.039 μL/mL. However, their MIC90 values were less than fluconazole against Candida isolates.

The results of this study suggest that P. ferulacea and P. uloptera essential oils might be used as new antifungal agents.

The present work aims to assess if insulin combined with phenolic fraction concentrates (PFCs) prevents diabetes-related cognitive impairments by controlling neuroinflammation in streptozotocin-induced diabetic rats exposed to chronic mild stress (CMS).

Directly after confirming the hyperglycemia, diabetic animals were treated with insulin combined with PFC and were exposed to 2 stressors/day for 12 weeks. Then, four cognitive tests were carried out to assess learning and memory performances. Finally, the rats were anesthetized, blood samples were collected for corticosterone and Tumor necrosis factor alpha (TNF-α) analysis, and the brain regions viz. striatum, hippocampus, and prefrontal-cortex of each hemisphere were dissected out for TNF-α analysis.

Both diabetes and stress could induce learning and memory impairments, which were more prominent in stressed diabetic animals, and significantly reversed by insulin treatment supplemented with PFC compared to the insulin monotherapy. Moreover, diabetic rats exposed to CMS displayed disturbances in glucose homeostasis as well as corticosterone secretion. These dysfunctions were linked to the significant increase of TNF-α in the blood as well as in the prefrontal cortex, hippocampus, and striatum. Insulin significantly ameliorated this inflammatory abnormality, while the supplemented treatment showed a significant effect, by stabilizing TNF-α to its normal levels in the hippocampus and in the blood when compared to insulin monotherapy.

Insulin supplemented with PFC has a favorable effect over insulin alone on inflammatory aberrations linked with type 1 diabetes and stress in animals, confirming the preference of the combined treatment over insulin for the management of cognitive impairment in stressed diabetic subjects.