Natural Products Journal, The - Volume 11, Issue 4, 2021

Channa striata (also known as Channa striatus) is an air-breathing freshwater snakehead fish that is well known in the Asian region for its medicinal properties, particularly in wound healing. It is recognised as a traditional medicine (TM), which can be served as alternative treatment method. With the advancement of technology, researchers have made a lot of progress in characterising the biomolecules of this fish. Various types of bioactive molecules have been identified in the fish, and their therapeutic effects are being studied. The C. striata have exhibited antibacterial, antinociceptive and effective wound recovery property through various pharmacology assays. It has been regarded as a source of traditional medicine that could complement modern medicine in promoting human health. The applications of C. striata extracts by practitioners in treating different illnesses are discussed. Besides, the approaches towards scarless wound in future applications involving the snakehead fish are also highlighted. Challenges and solutions to develop an aquatic-derived drug were also covered. The Channa striata extract as a natural product has shown great prospects for wound healing enhancement. Many biomolecules associated with antibacterial and antinociceptive properties, which are crucial for healthy wound recovery were identified in the species. Significant advances and researches in the region have successfully led to a better understanding of the species, which provide a promising future for drug development.

Epimedium sp. is a famous plant as sexual enhancer. In Chinese Pharmacopeia, Five species of Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum, and E. wushanense were recorded as Epimedium Herba (Yin Yang Huo). The aim of this review article was to evaluate the potential efficacy of E. brevicornum as a remedy for sexual dysfunction and infertility. For preparing of this manuscript, we searched in all accessible resources (PubMed, Science Direct, Wiley, Springer, and Google), books, thesis, and pharmacopeias. There are different traditional prescriptions containing E. brevicornum, which are recommended for the treatment of impotence and sexual disorders. Although, there is no clinical study on efficacy and safety of E. brevicornum on sexual functions, but animal and experimental analysis exhibited that E. brevicornum is an estrogenic plant and its flavonoid glycosides are inhibitors of phosphodiesterase 5 (PDE 5) and improved the erectile dysfunction, libido, impotence, sperm quality and fertility. Due to the lack of clinical study on the efficacy of E. brevicornum, designing the human clinical study on safety and efficacy of standard E. brevicornum can be the subject of future studies.

(±)-Indolizidine 209D is one of the alkaloids isolated from the skin secretions of certain neotropical frogs and exhibit a range of pharmacological properties, including blocking neuromuscular transmission. Therefore, the synthesis of indolizidine 209D and more complex derivatives, have been the subject of several publications. The preparation pathways of indolizidine 209D and its derivatives are the subject of this review. In this paper, some highly regio- and stereoselective functionalization process were reviewed through the synthesis of the optically active (±)-indolizidine 209D.

Gloriosa superba: L. (G. superba) is a perennial creeper and climbs up to 5-7 meters. It belongs to the Liliaceae family and is native to Africa and South-East Asia. It is also categorized as an endangered plant which may be due to its extensive use. Objective: The objective of the present review is to explore anticancer potential with other pharmacological activities of G. superba and its active constituents. G. superba has been reported to have many chemical constituents including colchicine, β- sitosterol, glumicolchicine, b-lumicolchicine, 2-OH-6-MeO-benzoic acid, glorisine, tannins, colchicoside, cornigerine, and many more. Most of them are effective against cancer, gout, arthritis, ulcers, bleeding piles, impotence, snakebites, skin diseases, and leprosy. G. superba has also been reported to possess pharmacological activities like anticancer, anti-inflammatory, antioxidant, abortifacient, anti-ulcerogenic, anti-helminthic and antimicrobial. The present review summarizes the anticancer potential of G. superba and its constituents. However, a detailed study is required to establish it as an effective anticancer drug.

Parasitic worm infections are a major health issue around the world, which cause numerous physiological damages in the patient's infected organ(s). The aim of this review was to investigate the anthelmintic properties of various medicinal plants. In this systematic review, all Randomized Controlled Trials (RCTs), quasi-experimental and experimental studies examining the anthelmintic effects were retrieved from databases, including Institute for Scientific Information (ISI) and PubMed from 1988-2019 by interesting keywords. In vitro and in vivo studies have demonstrated that many medicinal plants, including their compounds and derivatives, have anthelmintic properties through various Mechanisms Of Action (MOA). Examples of MOAs include paralysis of the helminths’ central nervous system, tegumental (outer body covering) destruction, interference with enzyme functioning, increased autophagy and apoptosis and reduction in cell viability and count. These actions lead to a reduction in the helminth ability to reproduce, decrease in egg count, inhibition of energy generation, damage to digestive tissues, lipid and ion accumulation, and change in and binding to different regulatory proteins and disruption of the helminth motor activity. These MOAs can also be used for the treatment of parasitic worms. Medicinal plants and their compounds have been the primary sources of new therapeutics, and are comparably more cost-effective than synthetic drugs and provide effective methods to combat parasitic worms that have entered into the human body. Therapists must take into account the effective dose of these compounds in treating the patients and also consider their overall health status, including comorbidities. There is an urgent need to conduct clinical trials using certain approaches, such as clinical interventional trials, to identify the effectiveness of herbal medicines in treating human host and zoonotic helminthic infections.

Background: The study aimed to compare the antimicrobial activity and cytotoxicity of saponin extracted from six sea-cucumber species, licorice, and ginseng to determine the most potent one. Methods: Antimicrobial activity assessed by well diffusion and agar dilution methods. The inhibitory effects of the tested extracts on cell growth of Liver (HePG-2) and breast (MCF-7) cell lines assessed by MTT [3- (4, 5- dimethyl thiazol-2yl) - 2, 5- diphenyl tetrazolium bromide] assay. Results: The results revealed that licorice extract presented higher antibacterial activity against Gram-positive bacterial strains than sea-cucumber extracts; but has comparable results for Gramnegative (Salmonella tyhimurium, Klebsiella spp, and Acinetobacter baumanii). Holothuria atra body wall and Bohadschia tubules have the highest antifungal effect against Candida albicans, Candida krusei, Candida famata, Candida glabrata, and Candida tropicalis. Sea-cucumbers are more potent against fungal strains than licorice and ginseng extract. Licorice and ginseng presented higher cytotoxicity against HePG2 and MCF-7 cell lines than sea-cucumbers. Conclusion: This study promotes the use of licorice extract as a better antibacterial substance than sea-cucumber extracts; however, the use of sea-cucumber extracts as antifungal agents than herbal extracts. Also, we support the utilization of licorice and ginseng as a cytotoxic agent instead of seacucumbers to stop the fishing of animals and consequently save it from extinction.

Background: Metribuzin (Mtz), a pesticide often used on vegetable crops to control broadleaf and grassy weed species has shown significant toxicity to humans and animals. Many plant extracts have been reported to have multiple biological properties. Ephedra alata extract might be useful in preventing and protecting the population from getting affected by metribuzin toxicity. Objective: The current study evaluates the protective effect of Ephedra alata aqueous extract against metribuzin (Mtz) pesticide induced adverse effects on biochemical parameters as well as oxidative stress in various tissues of rats. Methods: This study was conducted on 24 Albino rats, which were divided into three groups; the first served as a control, the remaining groups were respectively treated with metribuzin 1/5 of the LD50 (440 mg/kg b.w.) and a combination of Mtz and Ephedra alata aqueous extract at the dose level of 200 mg/kg b.w. for 50 days. Results: After 50 days of treatment, a significant increase in glucose levels was noticed in the metribuzin-exposed group compared to the control. Mtz exposure resulted in the increase in plasma urea and creatinine in rats, suggesting renal failure and caused also a significant induction of oxidative damage in tissues as evidenced by increased activities of AST, ALT and ALP, increased levels of malondialdehyde, decreased levels of reduced glutathione in Mtz group compared to the control. Conclusion: Ephedra alata aqueous extract at the dose level of 200 mg/kg b.w. supplementation has significantly reduced the adverse effects of metribuzin. These findings suggest that Ephedra alata extract may have protective effects by improving the antioxidant status in tissues and ameliorating the harmful effects induced by Mtz.

Background: Diabetic Nephropathy (DN), a microvascular complication of diabetes has been a significant health issue globally. However, theaflavin enriched black tea extract (BTE-TF) could restrain DN. Objective: The main objective of this exploration was to elucidate the effect of BTE-TF on DN, though the underlying mechanism remains unclear and requires further investigation. Methods: The tea leaves were fermented to get black tea extract. Total phenolic content and HPLC were carried out to determine the phenolic content and theaflavin in the extract. Streptozotocin induced diabetic rats were treated with 100, 200, and 400 mg/kg/day BTE-TF extract for 12 weeks. Biochemical parameters like blood glucose, creatinine, Blood Urea Nitrogen (BUN), triglyceride and antioxidant parameters of kidney tissue were measured. Histology, immunohistochemistry and TUNEL assay were performed to observe the effect of the extract with comparison to the standard drug (Metformin 200mg/kg/day). Result: Treated animals exhibited reduced blood glucose levels, blood urea nitrogen (BUN), creatinine, and serum triglycerides. Further, BTE-TF restored the histological alterations in the kidney. Chronic hyperglycaemia resulted in a significant increase in oxidative stress and pro-inflammatory cytokines of NF-kβ pathway. BTE-TF attenuated oxidative stress (p<0.01), inflammation (p<0.05) and apoptosis (p<0.05). Conclusion: This study suggests that BTE-TF exerts a protective role against diabetes-induced renal injury by ameliorating oxidative stress, inflammation, and apoptosis.

Background: The use of red propolis has antimicrobial, anti-inflammatory, antioxidant activity results, and provides local conditions that optimize events involved in the healing process, accelerating tissue repair. Objective: To evaluate the chemical composition, antioxidant activity, cytotoxic effects, and healing potential of Red Propolis Hydroethanolic Extract (RPHE) on the surgical wounds of cats submitted ovarisalpingohisterectomy. Methods: Chemical analyses of RPHE were carried out using HPLC-DADESI-MS/MS. Antioxidant activity was evaluated using the DPPH (2,2-diphenyl-1-picrilhydrazyl) method, and cytotoxicity was evaluated using the MTT colorimetric method. The healing effect of the extract was evaluated in 60 domestic cats (Felis catus) divided into three groups: GI: treated with topical application RPHE; GII: received topical application of commercial rifamycin-based solution, and GIII: treated with topical application of 0.9% NaCl physiological solution. Surgical wounds were evaluated for clinical, macroscopic, and histological aspects. Results: The RPHE showed 26 flavonoids and high antioxidant activity. Propolis extract had no cytotoxic effect on any of the cell lines tested. High cell viability percentages were observed, ranging from 80.0% to 94.4% for L929 fibroblasts and 78.0% to 91.5% keratinocytes (Hacat). Red propolis had a positive influence on the healing of wounds in cats submitted to ovarisalpingohisterectomy because it promoted less intense inflammatory response, rapid closure of the wound, early deposition of collagen and reepithelization. Conclusion: The RPHE presented rich in flavanoids, high antioxidant activity, did not exert cytotoxic effect and promoted the acceleration of healing of surgical wounds.

Background: Orthosiphon aristatus is a popular medicinal herb because of its pharmacological significance. Therefore, a lot of products formulated from the plant extract are available in the market. However, many phytochemicals in the plant extract are still remained to be unknown. Objective: The objective of this study was to profile phytochemicals from the plant extracts prepared using water and ethanol in a reflux system for comparison. Method: The commonly used analytical techniques of acetone precipitation (gravimetry) and vanillin assay (colorimetry) were used to estimate total saponin in the plant extracts. The low dielectric constant of acetone (20.7) was used to precipitate saponins. The phytochemicals in the plant extracts and their respective precipitates were then identified by LC-MS/MS. Results: Higher amount of precipitate was formed from ethanol extract than water extract. The results of LC-MS/MS revealed that not only saponins, but other phytochemicals, such as phenolic acids, flavonoids, terpenoids and aliphatic acids were also detected in the precipitates. In particular, ethanol extract and its precipitate were found to have higher flavonoids. Acetone precipitation could significantly increase the content of sagerinic acid and rosmarinic acid, as well as polyhydroxylated and polymethoxylated flavones from the water extract. Conclusion: Acetone precipitation is not specific for saponin, but also any phytochemicals which have lower solubility due to the lack of hydrogen bonding in high dipole moment medium of acetone. Gravimetric acetone precipitation had successfully profiled the phytochemicals in both highly complex water and ethanol based crude extracts.

Background: Sunset yellow is a commonly used synthetic food additive in various food beverages. Over usage of this colorant induces the anxiogenic behaviour in mice through oxidative stress. Vernonia cinerea reverses anxiogenic behaviour by counteracting oxidative stress. Objective: The study was designed to screen the protective effect of Vernonia cinerea extract against sunset yellow induced anxiogenic behaviour in mice through counteracting oxidative damage. Methods: The anxiogenic behaviour was induced by the administration of sunset yellow (20 mg/kg, p.o) for 30 days. Ethanol extract of aerial parts of Vernonia cinerea (EEVC) (400 mg/kg, p.o) was administered after 1 hour of sunset yellow treatment. Diazepam (1 mg/kg, p.o) was used as a reference drug for comparisons. Results: FT-IR studies of the extract were done by comparing with standards to determine the presence of phenols and flavonoids. Vernonia cinerea significantly improved the altered anxiogenic behaviour of sunset yellow treated animals. Significant increase in the brain antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and neurotransmitter Gamma-aminobutyric acid (GABA) level and decrease in the lipid peroxidation and glutamate neurotransmitter were observed in Vernonia cinerea treated group and also this extract reversed the hippocampus CA3 region abnormalities such as perivascular oedema, haemorrhage and severe vocalisation in sunset yellow group. Conclusion: Vernonia cinerea possesses significant antioxidant, antiradical and GABA enhancing effects against sunset yellow induced anxiogenic behavior in mice.

Objective: Diabetic Neuropathic Pain (DNP) is a common complication in both types of diabetes, which does not respond well to common pain medications. Asafoetida, an oleo-gum-resin extracted from Ferula asafoetida, is used as an analgesic, sedative, and antispasmodic in Iranian traditional medicine. Hence, the present study aimed to investigate the anti-neuropathic pain effects of asafoetida in streptozotocin-induced diabetic rats. Methods: Forty male Wistar rats were randomly divided into five groups. In four groups, diabetes was induced by intraperitoneal injection of a single-dose of streptozotocin (60 mg/kg). Three diabetic groups were treated once daily with asafoetida extract at doses 25, 50, and 100 mg/kg for 25 days. In all groups, the neuropathic pain was evaluated using behavioral tail-flick and von-Frey tests on days 0, 7, 14, 21, and 28. In addition, fasting blood glucose was also measured at the mentioned days. Key Findings: According to the results obtained from the behavioral tests, neuropathic pain was established in the diabetic rats on day 21. However, in comparison to untreated animals, the intensity of the pain (thermal hyperalgesia and mechanical allodynia) was significantly lower in groups receiving asafoetida extract (50 mg/kg, P<0.05 and 100 mg/kg, P<0.01). In addition, the extract could decrease fasting blood glucose in a dose-dependent manner (P<0.05). Conclusion: Ethyl acetate extract of asafoetida can prevent the development of neuropathic pain in diabetic rats. This effect may be, in part, due to the glucose lowering effect of asafoetida. However, further studies are needed to determine the possible mechanisms of action in relieving DNP.

Background: Long-term administration of valproic acid (VPA) is known to promote renal tubular injury mediated by an increase in renal oxidative stress. Recent evidence indicates that natural antioxidants are alternative to attenuate oxidative stress and kidney damage. Objective: This study was performed to investigate the protective effects of n-butanol extract of Rhanterium suaveolens, vitamin E (Vit E), and vitamin C (Vit C) against VPA induced nephrotoxicity in mice. Methods: Mice were randomly divided into 6 groups (n: 8) and treated daily for 12 days. They received VPA (300 mg/kg intraperitoneally (ip)), buthanolic extract (100 mg/kg), Vit E (100 mg/kg), and Vit C (16.66 mg/kg) 1h prior to administration of VPA. On day 13, blood and Kidneys samples were analyzed for biomarker levels and histopathological changes. Kidneys homogenates were used for the determination of oxidative stress parameters that include malondialdehyde (MDA), glutathione (GSH) level and Glutathione Peroxidase (GPx) activity. Results: Treatment with VPA showed a significant increase in the levels of serum creatinine, urea and malondialdehyde (MDA) and decreasing the enzymatic activity (GPx) as well as GSH levels in the kidney with marked necrotic epithelial cells and infiltration in kidney sections as compared to the control group. Pretreatment with the n-butanol extract of R. suaveolens, Vit C or Vit E 1 h prior to administration of VPA showed a significant decrease in the levels of serum creatinine, urea, and MDA, as well as an improvement in the antioxidant elements and histological changes compared to those previously seen in the group treated with VPA alone. Conclusion: It is concluded that n-butanol extract of R. suaveolens, Vit C and Vit E pretreatment effectively improved renal function and tissue oxidative damage caused by VPA.

Background: C. delpyi, C. decalvatus and C. caudatus are in the Euphorbiaceae family. The aerial parts, such as twigs, leaves and barks of these plants are used as traditional medicine such as anti-inflammatory, cytotoxicity, and antifungal properties. Objectives: The aims of this work were 1) to study the chemical composition of C. delpyi, C. decalvatus, and C. caudatus 2) to test the antibacterial, anti-HIV-1 RT, and cytotoxicity activities of crude extracts and pure compounds from these plants. Methods: Extraction, separation and purification of three plants were performed following chromatographic method. The biological activities, including antibacterial, anti-HIV-1 RT and cytotoxicity assay of three plants, were evaluated by the standard methods. Results: Phytochemical investigation of C. delpyi highlighted a new clerodane diterpenoid; crotondelpyitin A (1). The five known compounds were found, such as acetyl aleuritolic acid (2), 5- hydroxy-7,4′-dimethoxyflavone (3), and pilloin (4) in C. decalvatus and 3α-benzoyloxy-D while Afriedo- oleanan-27,16α-lactone (5), and bergenin (6) in C. caudatus. Compound 3 showed the most effective antibacterial activities with MIC in range <0.16 -1.25 mg/mL, and MBC in range 0.6 - >5.0 mg/mL. The six compounds were inactive with anti-HIV-1 RT. In addition, compound 4 was active for cytotoxic activities on FaDu and KKU-M213 at <4 μg/mL. Conclusion: The present study reveals that the Croton species are sources of diterpenoid-type compounds and a significant guide for further research of chemical constituents from these plants as potential medicines.

Background: The production of insecticidal proteins is one of the greatest vital direct defense responses in plants against the attack by phytophagous insects. One particular class of the entomotoxic proteins present in many plant species is lectins that is used against a wide range of important insects. Aim: The insecticidal activity of two lectins from seeds of white kidney bean (Phaseolus vulgaris) and soybean (Glycine max) on the growth, development and survival of the cotton leafworm, Spodoptera littoralis Boisd. (Lepidoptera: Noctuidae) was studied. Methods: Lectin products were isolated and purified using ammonium sulfate precipitation. Insecticidal activity, growth-inhibitory and physiological effects on the differential haemocyte count of lectin products were evaluated against S. littoralis. In vivo effects of lectin products on some S. littoralis enzymes were also determined. Results: Lectin contents in 250 g seeds were 700 and 500 mg in soybean and white kidney bean, respectively. The total protein concentrations were 160-163 and 118-120 mg/mL in soybean and white kidney bean, respectively. The insecticidal activity of lectin products exerted a strong effect on the larval weight gain and the reduction of the weight reached to 75.25%. Furthermore, the other developmental stages of pupation and adult formation were also affected. An elongated larval duration was noticed since larval duration was 24.8 days compared with control (12.0 days). Complete pupation (100%) was recorded in the control; however, a significant decrease in pupation was found to be 54.0% in treated larvae. Lectin products increased the average number of 123.9 haemocytes (123.9) compared to the control (94.4 haemocytes/field). In addition, lectin products inhibited the activity of total proteases, α-amylase, GST and total esterases. Conclusion: It can be concluded that the lectins have high potential in pest control strategies based on their activity towards the cotton leafworm, S. littoralis. These findings suggest that lectin products are interesting tools for integrated pest management in important agriculture crops.

Background: Plant derived compounds, naringenin and ellagic acid might interfere in MTT (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide) assay in the form of reducing the tetrazolium salt in the absence of cells. Objective: Effect of naringenin and ellagic acid in MTT assay. Methods: MTT assay has been performed in different conditions like, varying the concentration of phytocompounds, incubation time, and changing the media. Results: Ellagic acid at the concentration of 80 μg/ml showed maximum absorbance of 0.579 in the presence of RPMI media (Roswell Park Memorial Institute Medium) that has 10% newborn calf serum. Naringenin showed higher absorbance of 2.74 at 80 μg/ml in RPMI media that has 10% newborn calf serum. Naringenin and Ellagic acid had better ability to reduce the MTT in the presence of RPMI media than anhydrous ethanol. Conclusion: Naringenin reduced the MTT better than ellagic acid in RPMI-1640 medium. These results show the need to be cautious when choosing MTT assay to measure the metabolic activity of cells treated with phytocompounds.