Chemistry, biological activities and toxic effects of alkaloidal constituents of genus Delphinium - A mini review

The genus Delphinium is one of the essential members of the family Ranunculaceae. These species grow wild in North America, Europe, and Asia. They have demonstrated antioxidant, antimicrobial, and cytotoxic activities. Diterpenoid alkaloids are their main constituents and seem to be responsible for medicinal and toxic properties. The primary purpose of this paper is to review the therapeutic benefits of Delphinium species, chemical composition, and its medicinal uses, in addition to the reported toxic effects of these plants influencing different animals and humans.

Neuroprotective effect of ethanolic leaf extract of Commiphora caudata (Wight & Arn) against lipopolysaccharide-induced neurotoxicity in Wistar rats

Introduction: Commiphora caudata contains various essential phytoconstituents and is a potential medicinal plant used traditionally to treat various ailments such as neurodegenerative diseases. The present study aimed to evaluate the neuroprotective effect of ethanolic leaf extract of Commiphora caudata against the lipopolysaccharides (LPS) induced behavioral changes in rats. Methods: The in-vitro antioxidant potential was evaluated by 1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay methods. For in-vivo studies, the animals were pre-treated with ethanolic leaf extract of Commiphora caudata (EECC) at 200 and 400 mg/kg of b.w for 30 days, and neurotoxicity was induced with a single intraperitoneal injection of LPS 1 mg/kg, b.w on day 31. The neurotoxicity was evaluated with a chain of behavioral tests such as the Morris water maze test, radial arm maze, and choice reaction time (CRT) tests. At the end of the study, rats were sacrificed, the brain hippocampal region was removed, and the levels of acetylcholinesterase, nitric oxide, and protein were measured. Results: The IC50 value in the DPPH method was 71.58 ± 15.62 μg, and the total antioxidant activity of EECC was found to be 742.33 ± 14.57 μmol Fe (II)/g extract. In behavioral tests, animals treated with EECC at 200 and 400 mg/kg showed a neuroprotective effect in the Morris water maze test, an 8-arm radial maze test, and in the CRT test. Both doses reduced acetylcholinesterase, nitric oxide, and protein levels (P < 0.001), respectively. Conclusion: The present study results showed the promising neuroprotective effects of ethanolic extract of leaves of Commiphora caudata and its action against the LPS-induced cognitive impairment in rats.

Neuroprotective effect of methanolic extract of Sargassum wightii on rotenone-induced parkinsonism-like symptoms in Wistar albino rats

Introduction: The pathogenesis of Parkinson’s disease (PD) is multifactorial in which oxidative stress, neuroinflammation, and mitochondrial dysfunction are the leading factors. Currently, the antioxidant and anti-inflammatory agents of natural sources as neuroprotectants have raised much attention. The current study aimed to explore the neuroprotective effect of methanolic extract of Sargassum wightii in male Wistar albino rats against rotenone-induced PD. Methods: The rats were administered with rotenone (10 mg/kg orally) daily for 28 days to induce PD. S. wightii (200 mg/kg and 400 mg/kg) and levodopa+carbidopa combination (10 mg/kg) were administered to different groups of rats one hour prior to rotenone for 28 days. Behavioral parameters (akinesia, tremor, motor coordination, and locomotor activities) and body weight were recorded on days 14th and 28th of drug treatment. On the 28th day, the animals were sacrificed for the neurobiochemical analyses of brain tissue. Results: Rotenone treatment caused a significant reduction in behavioural parameters (P < 0.001), neurochemical deficits (P < 0.001), and elevation of oxidative stress markers (P < 0.001) in the brain. Pre-treatment with S. wightii at 200 mg/kg and 400 mg/kg doses significantly attenuated the rotenone-induced behavioral alterations and restored the mitochondrial NADH dehydrogenase activity and dopamine level in the striatum (P < 0.001). Moreover, 400 mg/kg of S. wightii restored the rotenone-induced increased oxidative stress markers like malondialdehyde (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) in the striatum (P < 0.01). Conclusion: S. wightii has provided a neuroprotective effect, probably by virtue of its antioxidant and dopamine restoring potential. Hence, it may offer a promising and new therapeutic lead for the treatment of PD but needs further research.

The cytotoxicity, anti-inflammation, anti-nociceptive and oral ulcer healing properties of coconut shell liquid smoke

Introduction: Coconut shell liquid smoke (CS-LS) from Cocos nucifera L. has been traditionally used by Indonesians as a natural preservative. Besides that, liquid smoke is also used as a medicine to treat various types of wounds. During the storage, liquid smoke resulting from pyrolysis is still questionable in relation to the oxidation process and changes in its properties and potentials. We observed the physical characteristics, components, toxicity, anti-inflammatory, anti-nociceptive properties, and effect in oral ulcer healing of CS-LS. Methods: Acidity was analyzed using a digital pH meter, density test was analyzed using a pycnometer, and the components were determined using gas chromatography-mass spectrometry (GC-MS). Eight concentrations of CS-LS (1%, 2%, 4%, 6%, 8%, 10%, 12%, and 14%) were tested on baby hamster kidney (BHK21) for the extract toxicity, carrageenan-induced rat paw edema for its anti-inflammatory properties, hot-plate test for its anti-nociceptive, and traumatized labial fornix incisive inferior for its oral ulcer healing. Results: The acidity of CS-LS was 2.296 and the density was 1.0102 g/mL. The major components analyzed were phenol (32.75%), 2-methoxy-phenol (17.45%), and furfural (13.09%). The CS-LS 100% and CS-LS 8% were the optimum concentrations for maintaining the BHK21 and increasing the number of fibroblasts in oral ulcer healing. The CS-LS 100% showed potent anti-nociceptive ability compared to other concentrations (P = 0.001), but not for the anti-inflammation properties. Conclusion: CS-LS is a promising natural herb for oral medicine, especially oral ulcer medicine.

Bioactivities, physicochemical parameters and GC/MS profiling of the fixed oil of Cucumis melo L seeds: A focus on anti-inflammatory, immunomodulatory, and antimicrobial activities

Introduction: Recently, the recovery of waste products from plants as a source of biologically active compounds has increased interest. Therefore, the current research aims to evaluate the anti-inflammatory, immunomodulatory and antimicrobial activities of the fixed oil of Cucumis melo L seeds, as well as to investigate its physicochemical parameters and chemical composition. Methods: Anti-inflammatory activity was examined using carrageenan-induced rat paw edema assay. The antimicrobial activity was assayed against Staphylococcus aureus, Micrococcus luteus, Enterococcus faecalis, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans by well diffusion method. The chemical composition of the oil was determined by gas chromatography/mass spectrometry (GC/MS), α-tocopherol was estimated by high-performance liquid chromatography (HPLC). Results: Cucumis melo oil had no toxicity and possessed a promising anti-inflammatory activity. Moreover, the oil exhibited a reasonable decrease in the pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and a significant increase in the anti-inflammatory cytokine (IL-10). The oil exhibited a reasonable antimicrobial activity against all tested organisms. The major identified compound in the unsaponifiable matter was (1-methyldodecyl) benzene (8.76%), while the major fatty acid was methyl linoleate (14.10%). The results of physicochemical characterization revealed the better quality of Cucumis melo oil. The amount of α-tocopherol in the oil was 23.5 μg/mL, which is considered a reasonable amount. Conclusion: These findings indicate that the fixed oil of Cucumis melo L seeds might be used as a safe natural anti-inflammatory, immunomodulatory and antimicrobial agent.

In vitro inhibitory potentials of ethanolic extract of Moringa oleifera flower against enzymes activities linked to diabetes

Introduction: Diabetes mellitus (DM) has been recognized as the seventh leading cause of global mortality; however, researchers seek alternative means to manage the menace. The current study sought to investigate antioxidant potentials, α-amylase, and α-glucosidase inhibitory activities of ethanolic extract of Moringa oleifera flower in vitro. Methods: Antioxidant properties of the extract were appraised by assessing its inhibition against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl (OH•), and hydrogen peroxide (H2O2) free radicals, as well as ferric reducing antioxidant power (FRAP), the antidiabetic activity was evaluated by α-amylase and α-glucosidase inhibition.Results: In this study, ethanolic extract of M. oleifera flower demonstrated a significant (P < 0.05) inhibition against DPPH free radical (43.57–83.56%) in a concentration-dependent manner, while FRAP (101.76 ± 1.63 mg/100 g), OH• scavenging ability (71.62 ± 0.95 mg/100 g), and H2O2 free radical scavenging capacity (15.33 ± 1.20 mg/100 g) were also observed. In the same manner, ethanolic extract of M. oleifera flower revealed a significant (P < 0.05) inhibition against α-amylase (IC50= 37.63 mg/mL) and α-glucosidase activities (IC50= 38.30 mg/mL) in the presence of their respective substrates in a concentration-dependent manner in comparison with acarbose. Conclusion: Ethanoic extract of M. oleifera flower could be useful as an alternative phytotherapy in the management of DM, having shown a strong antioxidative capacity and substantial inhibition against the activities of key enzymes involved in carbohydrate hydrolysis in vitro.

The effect of Quercus infectoria pair cream on the severity of episiotomy pain in nulliparous women

Introduction: Episiotomy is an incision in the perineal area during the second stage of labor to facilitate delivery. Complications of perineal injuries are one of the most important health issues. Oak pair has long been used experimentally to heal wounds and reduce pain. The present study was performed to investigate the effect of oak pair (Quercus infectoria) cream on pain due to episiotomy in nulliparous women. Methods: This double-blind clinical trial experimental study was performed on 120 nulliparous women in Asali hospital in 2018. Individuals were randomly divided into oak pair cream, placebo, and normal saline groups. Data were collected by demographic and midwifery information questionnaires and numerical pain scales. The creams were used by the participants every 12 hours for 10 days, and the pain intensity was evaluated before the intervention and on days 1, 5, and 10. Data analysis was performed by SPSS using chi-square, Kruskal-Wallis, and one-way analysis of variance (ANOVA) tests. Results: There was no statistically significant difference in pain intensity scores among the three groups of oak pair, placebo, and normal saline before the intervention (P = 0.20). Pain intensity on days 1, 5, and 10 after the intervention showed a significant difference between the three groups in favor of oak cream (P < 0.001). The results showed that there was a significant decrease in the mean pain intensity score of the oak pair receiving group over time (P < 0.001).Conclusion: Oak cream might be effective in reducing pain caused by episiotomy due to analgesic properties.

Efficacy and safety of Sahastara remedy for pain relief: A systematic review and meta-analysis of randomized controlled trials

The Sahastara (SHT) remedy is an herbal medicine that can be used as an alternative treatment for improving pain symptoms. The aim of this study was to evaluate the efficacy and safety of the SHT remedy for pain relief. PubMed, Scopus, ScienceDirect, TCI, and ThaiLis were systematically searched for relevant articles from inception to April 2021. We only included randomized clinical trials (RCTs) in which the efficacy and safety of the SHT remedy were compared with those of non-steroidal anti-inflammatory drugs (NSAIDs). Study selection, data extraction, and quality assessment were independently performed by two reviewers. The clinical therapeutic outcomes were the pain score, WOMAC score, Oswestry Disability Index score, 100 meters walk result, global assessment, and adverse events of the SHT remedy. The outcomes were assessed and pooled using a random-effects model. Heterogeneity was assessed using the I2 test. Four studies with 213 participants were included in the analysis. The efficacy of the SHT remedy was not different from that of NSAIDs in terms of the pain score (standardized mean difference [SMD] = -0.31; 95% CI = -1.26, 0.65; I2 = 91%), WOMAC score (SMD = 0.05; 95% CI = -0.30, 0.41; I2 = 0.0%), Oswestry Disability Index score (SMD = -0.41, 95% CI = -1.18, 0.35), 100 meters walk result (SMD = 0.31; 95% CI = -0.25, 0.87; I2 = 0.0%), and global assessment (relative risk = 0.85; 95% CI = 0.62, 1.16; I2 = 0.0%). Moreover, there were no statistically significant differences between the SHT remedy and NSAID treatment groups in terms of adverse events or liver function. This meta-analysis demonstrated that the SHT remedy is not different from NSAIDs in terms of clinical therapeutic efficacy and adverse events. However, larger and well-designed studies are needed to confirm this conclusion.

Two new flavonoids and anticancer activity of Hymenosporum flavum: in vitro and molecular docking studies

Introduction: Hymenosporum flavum (Hook.) F. Muell. is the sole species within the genus Hymenosporum is known for its antimicrobial activity. The current study aims to examine the prospective activity of H. flavum as a safe supporter of sorafenib (as a reference standard) against hepatocellular carcinoma (HCC). Methods: Isolation and identification of compounds were made by chromatographic and spectroscopic methods. A fingerprint for the plant extract was done using HPLC-MS/MS spectrometric analysis. The total plant extract was examined in vitro for HCC activity. The isolated flavonoids were examined for their cytotoxic activities using molecular docking studies against both RAF-1 and ERK-2, and the promising compounds were further examined in vitro using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results: Two new flavonols were isolated from the leaf extract of H. flavum (Hook.) F. Muell., quercetin-3-O-(glucopyranosyl 1→2 ribopyranoside) (1) and kaempferol-3-O-(glucopyranosyl 1→2 ribopyranoside) (2), accompanying other six known flavonoids (3-8), and identified via spectroscopic analysis. Moreover, HPLC- PDA/MS/MS spectrometric analysis revealed the presence of seventy phenolic metabolites. The cytotoxic activity of the plant extract confirmed its potential action on HepG2 cells indicated by the production level of lactate dehydrogenase (LDH) upon treatment compared with the normal cells. The isolated flavonoids were examined for their cytotoxic activity using molecular docking studies against both RAF-1 and ERK-2 as proposed mechanisms of their anticancer activities. Furthermore, compounds 1 and 3, which showed the best in silico results, were further examined in vitro using qRT-PCR. They exhibited promising inhibitory activities against both RAF-1 and ERK-2 gene expression. Moreover, they showed promising cytotoxic activities indicated by the MTT assay. Also, both of them improved the efficiency of sorafenib in targeting both RAF-1 and ERK-2 pathways suggesting synergistic combinations. Conclusion: Our findings showed the potential cytotoxic activity of H. flavum extract on HepG2 cells. Some isolated compounds (1 & 3) exhibited promising inhibitory activities against both RAF-1 and ERK-2 gene expression giving a lead future study for these compounds to be used in pharmaceutical preparations either alone or in combination with sorafenib.

The vasodilatory effects of medicinal herbs on the cardiovascular system: A systematic review

Vasodilators are drugs that induce or start the widening of blood vessels and are commonly applied to treat disorders with irregularly high blood pressure, including hypertension, congestive heart failure, and angina. The present study aims to systematically review the studies on the vasodilation effects of medicinal herbs. The study was done according to the 06- Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and registered in the CAMARADES-NC3Rs Preclinical Systematic Review and Meta-Analysis Facility (SyRF) database. Various English databases, such as Scopus, PubMed, Web of Science, EMBASE, and Google Scholar, were used to find publications about the vasodilation effects of medicinal herbs with no date limitation. The searched terms and keywords words were: "medicinal herbs", "medicinal plants", "vasodilator", "vasorelaxant", "hypertension", "high blood pressure", "vasodilation", "extract", "essential oil". Out of 1820 papers (up to 2020), 31 papers met the inclusion criteria and were reviewed. The most important medicinal plants with vasodilation/vasorelaxant activity belonged to the family Asteraceae (19.4%) followed by Zingiberaceae (9.7%). Aerial parts (30.5%), leaves (30.5%), followed by roots (11.1%) were the most common parts used in the studies. The findings showed that ethanolic extract (33.3%), followed by aqueous extract (22.2%) and methanolic extract (19.4%) was the frequency used extraction methods, whereas the essential oil (13.9%) and hydroalcoholic extract (8.3%) were the second most used herbal remedies. The results of the current review study revealed that the plant vasodilatory agents were might be used as an alternative and complementary source to treat hypertension as they had lower important toxicity. Nevertheless, more investigations, particularly clinical trials, are needed to clear this suggestion.