Current Bioactive Compounds - Volume 16, Issue 8, 2020

Objective: Helenalin is a natural anti-inflammatory agent that is proving its efficacy to treat various medical conditions. Though many plants are proving their effectiveness but their mechanisms are still not well understood. The objective of the review is to summarize various mechanisms of helenalin to treat inflammatory disorders and cancers, adverse effects, and avenues of further research. Methods: Structured research was carried out including Pub med, Science direct Medline, Research Gate and Google Scholar to find all articles published on helenalin. Various keywords used were “helenalin”, “Arnica”, “cancer”, “anti-inflammatory”, “cardiovascular”, “IBD”, “pharmacokinetics” etc. The aim of the review was to find out the problem prevailing in the data published to date which will help the researchers to investigate the molecule clinically. Results: Seventy articles are included in the review. Helenalin is found to cure chronic conditions like rheumatoid arthritis, ulcers and malignancies like stomach, colon, breast, larynx, lung and skin cancers via multiple mechanisms. These diseases do not proceed via a unilateral pathway. So, it can be a useful molecule to treat numerous diseases. Conclusion: This review article will help us to systemically analyze the wealth of information concerning the medicinal properties of helenalin and to recognize the gaps which have vetoed its pervasive application in the medical community.

Background: A plant is a reservoir of potentially useful active chemical entities which act as drugs as well as intermediates for the discovery of newer molecules and provide newer leads for modern drug synthesis. The demand for new compounds in the field of medicine and biotechnology is centuries old and with a rise in chronic diseases and resistance to existing drugs in the field of anti-infective agents, the chemicals obtained from plant sources have been an area of attraction. The whole plant has possessed multiple pharmacological activities. This is scientifically established by in-vivo and in-vitro studies. Methods: Various electronic databases such as PubMed, Science Direct, Scopus and Google were searched to collect the data of the present review. All the collected information is categorized into different sections as per the aim of the paper. Results: Fifty-six research and review papers have been studied and were included in this review article. After a detailed study, we provide a significant description of various phytochemicals present in Nyctanthes arbor-tristis Linn., which is responsible for various pharmacological activities. Twenty of studied articles gives a general introduction and ethnobotanical information about the plant, two papers contained microscopic detail of leaf and fruit. Twenty papers contained information about the phytoconstituents present in different parts of Nyctanthes arbor-tristis plant and fourteen articles reported pharmacological activities like antioxidant, anti-inflammatory, antiarthritic, antimicrobial and immunobiotic activity. Conclusion: This review explores the published research work comprising the ethnobotanical description of the subjected plant, distribution, phytochemical profile, and arthritis-related pharmacological activities.

Background: Olive oil and fruits are essential components of Mediterranean diets. The olive tree is a prevalent plant species and one of the important cultivated crops of the Mediterranean region. The present study aimed to evaluate the effectiveness of olive in achieving glucose homeostasis through the inhibition of carbohydrate metabolizing enzymes using in vitro models and also determine the chemical composition of olive oil by GC/MS. Methods: The chemical composition of olive oil was determined by GC/MS and its antidiabetic activity was assessed through inhibition α-amylase and α-glucosidase enzymes in in vitro models. Results: The olive oil analysis by GC/MS yielded 41 constituents amounting to 98.21% of total oil composition. Oleic acid, 3-(octadecyloxy) propyl ester (19.34%), arachidonic acid (11.25%), oleic acid (6.07%), Docosahexaenoic Acid (DHA) (9.50%), pentadecanoic acid (5.53%), palmitic acid (3.86%), and linoleic acid (3.13%) were the major components of olive oil. Olive oil and extract produce dosedependent inhibition of α-amylase and α-glucosidase enzymes. The IC50 values for olive oil, olive extract, and acarbose were found as 210.50±4.76, 121.8±3.18, and 91.04±2.16 μg/mL, respectively, against the α-amylase enzyme. The IC50 values for olive oil, extract, and acarbose were found as 204.3±3.41, 165.04±5.27 and 116.5±2.17 μg/mL, respectively, against the α-glucosidase enzyme. Conclusion: The result of this study concluded that olive oil has oleic acid and its ester derivatives as major constituents. The study findings also confirm the traditional claim of olive use in the treatment of diabetes mellitus.

Background: Lovastatin is a statin drug used for lowering cholesterol in those with hypercholesterolemia to reduce the risk of cardiovascular disease. It is a BCS class II drug i.e. it has low aqueous solubility and high permeability. Objectives: Improvement of solubility and in vivo efficacy was investigated by formulating binary solid dispersions. Methods: Binary solid dispersions of lovastatin were formulated in the current study using two polymers i.e. Soluplus and PEG 4000. Seven batches of solid dispersions were prepared (S1, P1, SP1, SP2, SP3, SP4, and SP5) via the solvent evaporation method. The prepared dispersions were evaluated for equilibrium solubility, FTIR, XRD, DSC, SEM studies, and further in vitro drug release were evaluated. The results revealed significant enhancement in the solubility of drug-using polymer hybrids as compared to that of individual polymer dispersion batches. Results: A significant solubility enhancement was observed with SP5 (approx 40 times) having a higher concentration of Soluplus. FTIR studies indicated no drug to polymer interaction. DSC studies revealed complete amorphization of polymer and also X-RD data is also in compliance with DSC results. In vitro drug release studies showed almost 100% release in 2h in polymer hybrid batches in comparison to individual polymer batch (S1 and P1). The best dissolution characteristics were observed in SP3 and SP5 which is also in compliance with solubility data. Further in vivo efficacy studies revealed a significant reduction in LDL, HDL, TG, AST, and ALT levels in comparison to pure drug lovastatin group and hypercholesterolemia control group. Conclusion: Hybrid polymer may be a prospective carrier system for the enhancement of solubility of BCS class II drugs.

Background: Progress in the developments of pyrimidine-coumarin moiety as an IDO inhibitor is still continuing with an outcome of the good scaffold as pyrimidine as well as coumarin individually for anticancer activity. Hence we proposed a suitable approach for the synthesis of pyrimidinecoumarin moieties in a combined form from the results of docking studies. Objective: As part of our ongoing research towards the development of novel cytotoxic agents, the synthesis and cytotoxic activity of a series of N'-(1-(6-methyl-2-oxo/thioxo-4-sub phenyl-1,2,3,4- tetrahydropyrimidin-5-yl)vinyl)-2-oxo-2H-chromene-3-carbohydrazide derivatives are discussed in this study. Methods: N'-(1-(6-methyl-2-oxo/thioxo-4-sub phenyl-1,2,3,4-tetrahydropyrimidin-5-yl)vinyl)-2-oxo- 2H-chromene-3-carbohydrazide derivatives were designed, synthesized and evaluated for cytotoxic activity. The structures were confirmed by IR, 1H NMR, C13NMR, Mass spectroscopy. All the synthesized compounds were evaluated using in vitro MTT assay against HeLa and HepG2 cell lines. Results: Compound 6g showed inhibitory activity against IDO with IC50 values at nanomolar range in docking studies and compounds 6g and 6f also showed significant cytotoxic activity on human cancer cell lines like HepG2 and HeLa using in vitro MTT assay. Conclusion: This work showed that the coumarin containing pyrimidine derivatives are found to be the most potent against IDO through docking studies and cytotoxic against cell lines compared with cisplatin. This might give the information for the development of new series of compounds against IDO.

Background: Algeria, by its vast terrestrial extent and its climatic variation, has an abundant, rich and varied flora in which it was counted many aromatic and medicinal species that provide bioactive compounds characterized by their broad biological activities. In this context, this work is based on the evaluation of the antimicrobial activity of Quercus robur L. leaves extracts (Family of Fagaceae). Methods: Firstly, the collected plant material was defatted; then, the extraction of tannins and saponins was carried out according to a standard protocol where the extracts obtained were tested on some uropathogenic microbial strains by disk diffusion method with the determination of the Minimum Inhibitory Concentrations (MICs) by broth macro-dilution method. Results: The extraction yield of the selective extracts was 7.93 and 16.94% for tannins and saponins, respectively. The antibiotic resistance profile of the tested strains showed a resistance relatively important to several antibiotics, namely amoxicillin +clavulanic acid and ampicillin for Escherichia coli, while Pseudomonas aeruginosa showed resistance to amoxicillin+clavulanic acid, amikacin, cefotaxime and ceftazidime. However, Staphylococcus aureus was susceptible to penicillin, gentamicin, ofloxacin and chloramphenicol. Antifungal susceptibility testing has been shown that Candida albicans was susceptible to amphotericin B, econazole and it was clinically categorized as intermediate to miconazole drug. For antimicrobial tests, the tannins and saponins extracts exhibited a low to strong inhibitory effect at tested concentrations lower than 30 mg/mL (ranged from no inhibition to an inhibition zone diameter of 17.5 mm), depending on dose levels and tested microbial strains. Conclusion: This activity is proportional to the tested concentrations, knowing that tannins extract was more active compared to saponins extract. For this, Q. robur could constitute an important source for drug discovery.

Background: To evaluate the antiulcer activity of ethanolic leaves extract of Saraca indica against ethanol, pylorus ligature and indomethacin in albino rats. Materials and Methods: Ulcer was produced by ethanol, pylorus ligature and indomethacin in albino rats. Five groups (n=6) of rats were orally pre-treated with carboxymethyl cellulose solution, and ranitidine (80 mg/kg) respectively. In ethanol induced ulcer, the animals were treated with 200 and 400 mg/kg b.w. ethanolic leave extracts of Saraca indica in 0.3% CMC solution, 60 minutes before oral administration of absolute ethanol to produce gastric mucosal injury. In indomethacin induced ulcer, the drug was administered orally at the dose of 30 mg/kg b.w. After 7-9 hours of administration of indomethacin (30 mg/kg); the animals were sacrificed with high doses of anesthesia. In the pylorus ligature method, volume of free acidity, gastric secretion, pH and total acidity were estimated. In all three models, the ulcer index and % protection were estimated. Results: The anti ulcer activity of ethanolic leave extracts of Saraca indica in ethanol, indomethacin and pylorus ligature models is evident from the significant (P<0.001) reduction in ulcer index. In pylorus ligature model, significant (P<0.001) reduction in total acidity gastric volume and increase in pH were observed when compared with the standard drug. Conclusion: Ethanolic leave extracts of Saraca indica were found to be significantly protective against ethanol, indomethacin and pylorus ligature induced gastric ulcers in the experimental albino rats. The result obtained suggest that ethanolic leave extracts of Saraca indica possesses significant anti-ulcer activity.

Objective: The aim of this study is the estimation of total phenolic and flavonoid contents and the evaluation of cytotoxic, hemolytic and antioxidant activities of the methanolic extract obtained from the species Nonea vesicaria (L.) Rchb. Methods: The total phenolic and flavonoid contents were quantified by Folin-Ciocalteu and trichloroaluminum methods, respectively. The cytotoxic effect was tested by Brine shrimp lethality assay and the hemolytic activity was assessed by spectrophotometric test on human erythrocytes. Moreover, the antioxidant activity was determined by seven different techniques. Results: The phytochemical screening revealed the presence of many classes of secondary metabolites, a moderate level of polyphenols, and a low content of flavonoids. The methanolic extract showed a significant cytotoxic effect with a value of LC50 at 35.7±0.5 μg/mL and induced hemolysis in a dosedependent manner with a value of EC50 at 175.6±0.08 μg/mL. The results of antioxidant activities indicated an important effect on nonpolar systems especially in ferric thiocyanate test and β-carotene bleaching inhibition assay. Conclusion: The methanolic extract of N. vesicaria could constitute an important source of antioxidant and cytotoxic compounds but prudent use is recommended in order to reduce the adverse effects related to the possible hemolysis.

Background: Banisteriopsis campestris is a Malpighiaceae, also known as “cipó-prata” or “murici”. There are some reports about the use of this plant in folk medicine. Objectives: The aim of this study is to test the Essential Oils (EOs) from leaves, stems, and roots of B. campestris for antibacterial, antifungal, antioxidant, and antiprotozoal activities and the inhibition of glycation and cytotoxicity on Vero cells. Methods: The plant was collected and the essential oil was obtained and tested for antibacterial, antifungal, antioxidant, and antiprotozoal activities and the inhibition of glycation and cytotoxicity on Vero cells, using the more adequate methods to achieve the objectives. Results: The EOs inhibited the growth of aerobic and anaerobic oral bacteria. The root oil presented the highest antibacterial activity with MIC levels ranging from 12.5 to 100 μg mL-1. The three EOs showed antiprotozoal activity against Leishmania amazonensis. The stem and root EOs presented low cytotoxicity to Vero cells. The roots and stem oils showed inhibition of glycation above 50%, with stem oil with of 79.11%. The compounds identified in the leaf EOs were palmitic acid (22.98%), phytol (22.98%), and triacontane (14.88%); in the stem–palmitic (49.79%), linoleic (11.63%), oleic (4.83%), and palmitoleic (4.15%) fatty acids; in the root–palmitic acid (57.39%), linoleic (10.38%), and oleic acids (5.47%). Conclusion: The results presented indicate that the EOs have remarkable antioxidant properties and potential antimicrobial activity and confirm the essential oils of B. campestris as an alternative source of medicinal substances.

Background: Glycyrrhiza glabra L. is an important medicinal plant endowed with various pharmacological virtues. This study aimed to investigate the antioxidant, antibacterial, and anticholinesterase activities of the Algerian Glycyrrhiza glabra L. roots extracts. Methods: The chemical composition of both chloroformic (LCh) and ethyl acetate (LAE) extracts were analyzed by RP-HPLC-PDA and 1H NMR spectroscopy. The antioxidant activity was evaluated using hydrogen atoms transfer methods (DPPH) and single electron transfer (ABTS and CUPRAC assays). The antibacterial activity was realized against different strains via the Minimal Inhibitory Concentration (MIC), when the anticholinesterase activity was performed through the acetylcholinesterase and butyrylcholinesterase enzymes inhibition. Results: The chemical analysis revealed the presence of phenolic acids (gallic acid, p-coumaric acid) and a hydroxycinnamic compound (ferulic acid). However, flavonoids were represented by quercetin, rutin (flavonol), and glabridin (isoflavane). The 1H NMR of the L4 fraction from LCh extract allowed to characterize the structure of glabridin. The antioxidant assays revealed that LCh extract is the best among other extracts with IC50 DPPH of 33.94 μg/mL, IC50 ABTS of 3.45 μg/mL and CUPRAC A0.5 of 21.78 μg/mL. The LCh extract displayed an effective antibacterial activity with MIC’s of 19.5 μg/mL against seven gram positive and negative bacteria strains. The same extract showed a potent butyrylcholinesterase inhibitory activity with IC50= 4.72 ± 0.72 μg/mL, which is too strong than the standard drug. Conclusion: The study demonstrated that G. glabra root extracts had a high antibacterial, and free radical scavenging. It was also able to inhibit cholinesterase enzymes, which confirm the effectiveness of phytoconstituents present in the plant, especially flavonoids.

Background: Mimosa caesalpiniifolia Benth. (Mimosaceae) is a native plant from Brazilian Caatinga/Cerrado used in the traditional medicine. The aim of this work was to investigate the chemical composition and the antileishmanial activity of the inflorescences from M. caesalpiniifolia. Methods: The ethanolic extract from M. caesalpiniifolia inflorescences was submitted to fractionation in silica gel chromatography column, and the known structures were elucidated using spectroscopic methods. The antileishmanial activity of the EtOH extract and pure compounds was evaluated against the promastigote forms of Leishmania amazonensis. Results: In this study, the EtOH extract from M. caesalpiniifolia inflorescences (IC50 = 74.52 μg mL-1) and lupeol (IC50 = 15.40 μg mL-1) demonstrated significant inhibition of the growth at 48 h for promastigote forms of L. amazonensis when compared with Glucantime® (IC50 = 1190.21 μg mL-1), a reference drug. Moreover, the cytotoxicity evaluation of EtOH extract of M. caesalpiniifolia inflorescences against murine peritoneal macrophages was also determined. Then, the selectivity index shows that the EtOH extract of M. caesalpiniifolia inflorescences is more toxic to the parasite than mammalian host cells. The chemical characterization of the ethanolic extract from M. caesalpiniifolia inflorescences resulted in the identification of fatty acids and isoprenoids as lupeol acetate, lupeol, β-amyrin, a mixture of steroids and a mixture of fatty acid triterpenyl esters. 3-O-Acyl triterpenoids are being reported for the first time in M. caesalpiniifolia. Conclusion: The EtOH extract of M. caesalpiniifolia inflorescences is a rich source of triterpenoids and a promising natural product against leishmaniasis.

Background: Nowadays, bioactive moieties of plants are gaining attention amongst the masses to mitigate lifestyle related dysfunctions owing to their safe nature and functional properties. Objective: Considering phytochemistry and cost-effectiveness of cabbage, the current project was designed to probe the antioxidant capacity of locally grown green and red cabbage. Methods: The total polyphenols and free radical scavenging ability of red and green cabbage were determined using spectrophotometer while HPLC analysis was carried out to further fractionate phenolic acids and flavonoid constituents. Apart from this, antioxidant vitamins including vitamin C tocopherol and β-carotene were also detected using HPLC system. Results: The red cabbage showed higher amount of total polyphenols and flavonoids (224.37±6.96 & 219.15±10.30 mg/100g F.W.) than green cabbage (58.41±3.01 & 34.04±1.06 mg/100g F.W.) along with the existence of anthocyanins (69.86±4.12 mg/100g F.W.) in red cabbage. Comparative HPLC analysis regarding antioxidant moieties showed significant proportion of kempferol (171.10±5.99 mg/100g F.W.) followed by vitamin C (139.07±2.23 mg/100g F.W.) in red cabbage however, vitamin C (121.46±3.28 mg/100g F.W.) was found as the major antioxidant in green cabbage. The red cabbage depicted higher free radical quenching and reducing ability in contrast to green cabbage using DPPH (1, 1-diphenyl-2-picrylhydrazyl), ABTS [2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid)], FRAP (ferric reducing antioxidant power) and PFRAP (potassium ferricyanide reducing antioxidant power) and H2O2 scavenging ability assays. Conclusion: In the nutshell, red cabbage showed better free radical scavenging ability as compared to green cabbage based on variation and quantification of antioxidant indices.

Background: An upsurge in the number of antibiotic-resistant microbial infections has warranted the discovery and development of new antibiotics. This is a matter of great concern for effective therapy for a search of novel antimicrobial agents. Literature has a number of reports of involvement of oxidative stress due to an imbalance between the generation and neutralization of free radicals in many diseases. Heterocyclic compounds have been involved in the treatment of various disorders. Benzothiazole is one such heterocyclic nucleus having benzene ring merged with the thiazole ring. Among the various substitutions possible in this nucleus, substitutions at position-2 have already been reported with potential bioactivities. Thus, different substituted compounds have been synthesized which could serve as antimicrobials and antioxidants. Methods: Benzothiazole derivatives (B1-B7) were synthesized by two-step reactions and the structures were confirmed through infrared, mass and NMR spectroscopy. The compounds were evaluated for in vitro antioxidant and antimicrobial activities using standard methods. Results: The results of antibacterial and antifungal activity showed that compound B4 exhibited maximum activity against all the tested strains of microorganisms with the zone of inhibition 17.1-18.5 mm and MIC value 1.1-1.5 μg/mL. Compound B5 exhibited potent antioxidant activity. Conclusion: The compounds substituted with halogen on the aryl ring showed increased antimicrobial activity as seen in the case of compound B4 (6-fluoro). The compounds substituted with a hydroxyl group (B5) exhibited good antioxidant activity.

Background: Valerian, also known as Setwall, Baldrianwurzel, or Phu is an herbaceous perennial plant from Europe and Asia, ubiquitously dispersed in almost all countries with a pH of 6-7. Valeriana officinalis is often used to treat sleep disorders, anxiety, fatigue, seizures, epilepsy, and depression as traditional medicine for 2000 years. The main constituent of Valeriana officinalis is Valerenic acid with hydroxyl and acetone group derivatives. Valerenic acid has anxiolytic, tranquilizing, and sleep-inducing effects that have been demonstrated in both animal studies and clinical trials. Valerenic acid inhibits catabolism-enzyme induced breakdown of Gamma-Aminobutyric Acid (GABA) in the brain resulting in sedation. Gamma-aminobutyric acid is the most important brain inhibitory neurotransmitter with key roles in the regulation and function of the central nervous system. The sedative effect of Valerian extract is facilitated by the GABAA receptor β3 subunit. GABRB3 gene is a ligand-gated ion channel that encodes the GABAA receptor β3 subunit. GABRB3 also functions as a receptor for diazepam and other anesthetic drugs (i.e. phenobarbital). Valerian influences the presynaptic component of GABA-ergic neurons that affect the release of synaptic GABA. Valerian also inhibits GABA reuptake and GABA catabolism by inhibiting the enzyme GABA transaminase. On that basis, this study aims to determine the effect of valerian extract on GABRB3 gene mRNA expression and sedative effect in BALB/c mice. Objective: This is an experimental study using an animal model, with a posttest-only control group design to determine the effect of Valerian extract on GABRB3 gene mRNA expression and sedative effect in BALB/c mice. Methods: Twenty selected BALB/c mice were randomly allocated into four groups; each group consisting of 5 mice. Group A (negative control) was given 5 ml of aqua dest (distilled water). Group B (positive control) was given 0.025 mg/10 g of diazepam. Group C (treatment group 1) was given 2.5 mg/10 g of Valerian extract, and group D (treatment group 2) was given 5 mg/10 g of Valerian extract. The drugs were administered for seven days through a gastric gavage. Rotarod test was performed on the seventh day. A blood sample of 1 ml was taken on the first day before drug administration and after the rotarod test on the seventh day to be analyzed using RT-PCR. Results: GABRB3 gene mRNA expression showed a significant increase in group B, C, and D (p <0.0001). There was a significant difference between group C and D. The examination of motor coordination functions (Rotarod test) showed a significant difference (p <0.05) between group A and group B, between group A and group C, and between group A and group D. There was no significant difference between group B and both group C and D. Conclusion: GABRB3 gene mRNA expression was increased significantly after the administration of Valerian extract. Based on the Rotarod test, Valerian extract and Diazepam had a clinically similar sedation effect. A higher dose of Valerian extract does not yield a higher level of GABRB3 gene mRNA expression nor sedative effects.