Natural Products Journal, The - Volume 10, Issue 5, 2020

Background: Medicinal plants have been used to treat diseases for centuries. They are important sources in terms of their pharmacological effects and also have many microbial agents. Recently, the development of drug resistance has begun to spread in human pathogens against used antibiotics and this has led to new research for novel antimicrobial substances from natural products containing plants. Objective: The purpose of this review is to determine the antimicrobial activity of pure phenolic compounds isolated from medicinal plants, to evaluate how molecular structures of these compounds affect the activity, and to provide to the readers a source for future studies on natural antimicrobial agents. Methods: Relevant information was gathered from scientific engines and databases (Google Scholar, Web of Science, Scifinder, Science Direct, Scopus, Wiley Online Library, PubMed, Taylor & Francis online) using different keywords. Antimicrobial activity research was selected especially on pure phenolic compounds. Results: Numerous phenolic compounds were isolated from plants/plant extracts and were shown to prevent the growth of bacteria and fungi and their Minimum Inhibition Concentration (MIC) and inhibition zone values were given in detail. Conclusion: This review revealed that phenolic compounds found in medicinal plants have different antimicrobial activity according to their changes in the molecular structure.

Background: Benign Prostatic hyperplasia (BPH) is known as a disease prevalent in men after the age of 50 years old. Ninety percent of men with the age of 80 years and over have BPH. BPH is associated with functional problems like dysuria, nocturia, polyuria, urinary incontinence and recurrent urinary tract infections. Urtica dioica or nettle is a popular medicinal plant for management of BPH in men. Objective: This article evaluates the efficacy and safety of nettle and its related possible mechanisms in the management of BPH. Methods: For the preparation of this manuscript, all the information was gathered from accessible and inaccessible resources (Web, Books, Thesis, etc.). Results: The results of preclinical and clinical studies confirmed the efficacy of nettle roots extracts (methanol, ethanol, and petroleum ether) in the improvement of BPH in term of IPSS score, and patient's life quality. An increase in mean and maximum urinary flow rates and a reduction in prostate volume and residual urine level were observed after treatment with nettle extract. Nettle roots should be used for 6-12 months as its use is possible for a long time without any serious adverse effects. Conclusion: Designing the clinical trials to compare the efficacy of different extracts from roots or leaves and investigation of molecular mechanisms of action could be the approaches for future.

Background: Abrus precatorius L. (A. precatorius) is a valuable plant from the family Fabaceae which is a pea family. It is commonly known as Gunja or Jequirity, significantly found throughout India mainly Himalaya to Southern India and Ceylon. It is considered a poisonous plant due to the presence of abrin. Objective: A. precatorius has many pharmacological and biologically active constituents, such as alkaloids, glycosides and flavonoids situated in different parts of the plant. The objective of this review is to provide a retrospective study based on its anticancer potential. Results: Recent studies of A. precatorius are based on the isolation, characterization, and pharmacological evaluation of different secondary metabolites. These constituents possess significant cytotoxic properties against various cancer cell lines including breast, lung, liver, ovarian, prostate and leukaemia. A. precatorius is also reported to have anti-diabetic, anti-microbial, abortifacient, antioxidant, anthelmintic activity, antifertility, nephroprotective, and immunomodulatory activities. Conclusion: The present review summarizes the anticancer potential of A. precatorius and its constituents. However, extensive research is required to establish it as a potent chemotherapeutic agent.

Background: Hypoxia and anoxia are dangerous and sometimes irreversible complications in the central nervous system (CNS), which in some cases lead to death. Objective: The aim of this review was to investigate the neuroprotective effects of medicinal plants in cerebral hypoxia and anoxia. Methods: The word hypox*, in combination with some herbal terms such as medicinal plant, phyto* and herb*, was used to search for relevant publications indexed in the Institute for Scientific Information (ISI) and PubMed from 2000-2019. Results: Certain medicinal plants and herbal derivatives can exert their protective effects in several ways. The most important mechanisms are the inhibition of inducible nitric oxide synthase (iNOS), production of NO, inhibition of both hypoxia-inducible factor 1α and tumor necrosis factor-alpha activation, and reduction of extracellular glutamate, N-Methyl-D-aspartic and intracellular Ca (2+). In addition, they have an antioxidant activity and can adjust the expression of genes related to oxidant generation or antioxidant capacity. These plants can also inhibit lipid peroxidation, up-regulate superoxide dismutase activity and inhibit the content of malondialdehyde and lactate dehydrogenase. Moreover, they also have protective effects against cytotoxicity through down-regulation of the proteins that causes apoptosis, anti-excitatory activity, inhibition of apoptosis signaling pathway, reduction of pro-apoptotic proteins, and endoplasmic reticulum stress that causes apoptosis during hypoxia, increasing anti-apoptotic protein, inhibition of protein tyrosine kinase activation, decreasing proteases activity and DNA fragmentation, and upregulation of mitochondrial cytochrome oxidase. Conclusion: The results indicated that medicinal plants and their compounds mainly exert their neuroprotective effects in hypoxia via regulating proteins that are related to antioxidant, anti-apoptosis and anti-inflammatory activities.

Background: The presence of phenolic compounds is common in Urticaceae. However, only one report of the isolation of an apigenin in the Pourouma genus is available. Pourouma guianensis occurs widely throughout Brazil, mainly in the Southeastern region, and is popularly known as “pitinga”. The chemical profile of P. guianensis is marked by the presence of steroids and triterpenes. Objective: This study carried out the characterization of phenolic substances using UPLC-DAD-MS separation, in order to increase the chemical knowledge on the Pourouma genus. Methods: The extract was analyzed by UPLC-DAD-MS using a C-18 column, DAD detector at 190- 400nm and ESI-Q-TOF mass spectrometer. The solvent system consisted of water with 0.1% formic acid (phase A) and acetonitrile with 0.1% formic acid (phase B). Results: The extract analysis identified the presence of ten compounds: two aryl propanoids (5-Ocaffeoylquinic acid and 3-O-feruloylquinic acid) and eight glycosylated flavones derived from apigenin, luteonin, and chrysoeryol (vicenin 2, saponarin, orientin, isoorientin, isoschaftoside, schaftoside, isovitexin, and isoscoparin). Conclusion: The developed UPLC-DAD method was proven to be an efficient tool for the separation of phenolic mixtures and the UPLC-DAD-MS analysis enabled the identification of these compounds, reported for the first time in Pourouma genus.

Background: Spilanthes acmella Murr. is included in Asteraceae family which is used as a traditional remedy for tooth-aches, and originated from Africa, America, Borneo, India, Sri Lanka, Bangladesh, China, Japan, Thailand, and Indonesia. The present research aims to isolate the amine derivative from the ethyl acetate layer of this plant and to evaluate the isolated compounds of alkaline phosphatase activity as a sign of bone formation. Methods: The air-dried plants of Spilanthes acmella Murr. were extracted with methanol, then partitioned with n-hexane and ethyl acetate successively by using liquid-liquid extraction, and then the chromatographic techniques were repeated, such as silica gel, octadecyl silylated silica gel, and HPLC. The isolated compounds were determined by spectrometric analysis using ultraviolet, infrared, high-resolution electrospray ionization mass spectrometry, 1D and 2D NMR. Results: Benzenepropanoic acid, 4 hydroxy-2-oxo-3 piperidinyl ester (1), was isolated from the ethyl acetate layer of the whole plants of Spilanthes acmella Murr. together with dendranthemoside A (2), uridine (3), icariside B2 (4), chicoriin (5), dendranthemoside B (6), and ampelopsisionoside (7) from their butanol layer. Conclusion: An amine derivative, a benzenepropanoic acid that determined as 4 hydroxy-2-oxo-3 piperidinyl ester (1) was isolated and reported for the first time from the ethyl acetate layer of Spilanthes acmella naturally. All the isolated compounds from this plant stimulated alkaline phosphatase activity as a mark of bone formation up to 128%.

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Material and Methods: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

Background: Chinese cabbage or Brassica oleracea L. var. pekinensis is an edible leafy green vegetable in the family of Brassicaceae. Ethnopharmacological studies have shown that the juice of cabbage leaves is commonly used in the treatment of gastrointestinal disorders, irritable bowel syndrome, minor cuts and wounds and mastitis. Objective: This study was aimed to examine the gastroprotective effect of Chinese cabbage (Family: Brassicaceae) juice in rats by using ethanol-induced gastric ulcer model. Methods: Thirty albino male Sprague Dawley rats (150 ± 20 g) were divided into 6 groups with five rats (n = 5) in each group. The normal control group was treated with distilled water while the positive control group was intragastrically administered with omeprazole (20 mg/kg). Cabbage juice at 500 mg/kg was given orally to three experimental groups for 1-day, 7-day and 14-day, respectively. Ethanol (70 % v/v) was orally treated to all rats one hour after the last dose treatment except the normal control group. Results: Results obtained showed that repeated consumption of cabbage juice for 7 days and 14 days exhibited an increase in accumulation mucus and in the levels of superoxide dismutase (SOD), glutathione- s-transferase (GST) and glutathione peroxidase (GSH-Px) as well as a reduction in gastric lesion area induced by ethanol compared with the ulceration control group. Conclusion: In conclusion, the gastroprotective effect of Chinese cabbage juice could be associated with its ability to increase endogenous antioxidant activities of SOD, GST and GSH-Px and mucus secretion in rat stomach.

Background: Tubular calyx of flowers of Nyctanthes arbour-tristis contains an apocarotenoid crocin, a major constituent present in saffron stigma. The flowers of N. arbortristis are readily available, hence can be an economic substitute for saffron. Lutein from flowers of Tagetes patula, is another carotenoid which is a popular antioxidant. Objective: Oxidative stress is a major contributor to the process of aging. Carotenoids are powerful antioxidants. Hence, the study was carried out to evaluate anticollagenase activity and antielastase activity using gene expression study in Human dermal fibroblasts. Methods: Crocin was isolated from the tubular calyx of Nyctanthes arbortristis using flash chromatographic technique and lutein was isolated using column chromatography. Anticollagenase and antielastase activity of crocin and lutein were carried out using collagenase from Clostridium histolyticum as enzyme and porcine pancreatic elastase. Cytotoxicity of crocin and lutein was determined in Human Dermal Fibroblast cell line (HDF) through MTT assay. In gene expression study, the HDF Cell line was inoculated with Crocin (450 and 250 ppm) and lutein (100 and 50 ppm) separately for 24 hrs and the m-RNA expression levels of COL Type-1 and elastin were determined using RT-PCR. The results were compared with standards. Result: Crocin and lutein both showed inhibition of collagenase and elastase enzyme which are responsible for aging process. The cytotoxic concentration CTC 50 (ppm) for Crocin and lutein was found to be 790.2 ppm and 137.14 ppm. Gene expression study on crocin rich extract of Nyctanthes arbortristis showed upregulation of both collagen and elastin gene whereas lutein rich extract having concentration100 μg/ml showed up regulation by 0.02 fold and concentration 50 μg/ml showed down regulation. Conclusion: In vitro collagenase and elastase enzyme study and Gene expression study showed that these carotenoids are potential antiageing agents which can be substituted to synthetic cosmeceuticals as well as saffron.

Objective: The aim of the study was to evaluate the hypolipidemic and antioxidant properties of aerial parts aqueous extract of Warionia saharae (APAE of W. saharae) in normal and streptozotocin (STZ) induced-diabetic rats. Additionally, the quantitative and qualitative analysis for the presence of different phytochemical constituents in the APAE of W. saharae was performed. Methods: The effects of oral administration of APAE of W. saharae (5 mg/kg) on the plasma Total Cholesterol (TC) and triglyceride (TG) levels were measured in both normal and diabetic rats. Moreover, the antioxidant capacity was realized by the method of DPPH. Total polyphenol as x of the APAE of W. saharae were determined. Results: APAE of W. saharae showed a strong hypolipidemic and antihyperglycemic effects both in normal and in STZ induced diabetic rats. On the other hand, APAE of W. saharae showed a potent antioxidant activity and revealed inhibitory activity. Moreover, the quantitative determination of total polyphenol and flavonoid contents showed high contents of these phytochemicals. Concerning the qualitative analysis several classes of chemicals have been found. Conclusion: APAE of W. saharae (5 mg/kg) shows the potential cholesterol and glucose lowering activity as well as antioxidant properties in both normal and STZ-induced diabetic rats.

Background: The current research aimed to explore secondary metabolites and antibacterial activity against bacterial agents associated with bovine mastitis from extracts prepared from the peel of fruits of Punica granatum L.. Mastitis is an inflammation in the mammary gland mainly due to infection of bacteria and can be presented clinically or subclinically. The infectious bovine mastitis disease is associated with the reduction and changes in the composition of the milk, as well as in the early disposal of the animal. Objective: We describe the bactericidal activity of ethanolic extracts of the fruit peel of P. granatum, against etiological agents of bovine mastitis (Escherichia coli, Staphylococcus aureus and Streptococcus agalactiae). Method: The bactericidal activity was evaluated according to the standards of the European Committee for Antimicrobial Susceptibility Testing and by the broth microdilution methodology according to the standards of the Clinical and Laboratory Standards Institute. The fruit peel extracts of P. granatum were prepared with ethanol solvent (90%). Results: The best results of total inhibition of bacterial growth of the three strains tested were obtained with the concentrations of 75mg/mL of the extract after 1 and 3 hours of treatment. Cell membrane integrity analysis by flow cytometry showed that 1 h of contact there was loss of integrity of the wall and cell membranes. Conclusion: We can suggest that the ethanolic extract of the fruit peel of P. granatum can be an important natural coadjutant compound in the treatment of mastitis as well as being used in the formulation of sanitizers.

Background: Traditional knowledge has been a legacy of the past to the present. Barks of Ficus hispida Linn. and leaves of Ficus pomifera Wall. (Moraceae) have been used traditionally for the treatment of diabetes in North-east India and many other places. As many drugs have been developed from traditional plants, the authors have taken up the plants for the study of hypoglycemic activity. Objective: To investigate the hypoglycemic activities of the triterpenoids isolated from the plants and their antioxidant activities. Methods: The bioactive compounds were determined by biochemical analysis, antioxidant activity using DPPH method. Hypoglycemic activity was detected using glucose tolerance test in normal rats and alloxan induced diabetic rats with Gliclazide as standard. Results: The biochemicals and trace elements were present in appreciable amounts. Triterpenoids, (1-5), from F. pomifera and 19-hydroxyphlogacantholide (6), 3-O-[ß-D-glucopyranosyl-(1’→2’)-α- L-rhamnopyranosyl-phlogacanthoside] (7) and galanolactone (8) along with stigmasterol (9), stigmasta- 5,22-dien-7-on-3ß-ol (10), 5-(decahydro-1,1,4a-trimethyl-6-methylene-5-yl)-3-methylpent-2- enal (11), stigmasterol glucoside (12) and stigmast-4-en-3-one (13) from F. hispida Linn., respectively, were isolated. The different extracts of the barks and leaves of these plants along with the isolated compounds had antioxidant and hyploglycemic activities. Conclusion: The five triterpenoids (1-5) were isolated from the methanol extract of the leaves of F. pomifera, and compounds (6-13) were isolated from the chloroform extract of the barks of F. hispida. Methanol extract of the leaves of F. pomifera and the chloroform extract of the barks of F. hispida; compounds (1-13) isolated from these two plants reduced DPPH free radicals in a concentrationdependent manner. It was also observed that the methanol and chloroform extracts of the plants, F. pomifera and F. hispida respectively, and the compounds (1, 6 & 7) exhibited anti-diabetic properties and also caused a highly significant reduction in the blood glucose levels of normal rats.

Background: Nowadays, the application of several and natural preservatives in small quantity is a more preferred approach. In this regard, one of the effective methods is the formation of nanoemulsion of essential oils. Objective: The objective of this study was to compare the in vitro antibacterial activities of cinnamaldehyde (CIN) and Zataria multiflora essential oil in conventional (ZEO), nanoemulsion (NZEO) and fortified nanoemulsion (NZEOC) forms against common foodborne pathogens. Methods: Firstly, the Zataria multiflora essential oil was analyzed by GC-MS. The nanoemulsion of Z. multiflora essential oil was then prepared alone and fortified with cinnamaldehyde. Finally, their antimicrobial activity against Listeria monocytogenes, Staphylococcus aureus, Salmonella enteritidis and Escherichia coli was evaluated. Results: Based on the results, carvacrol (36.62%) was found to be the most important compound of essential oil. In disc diffusion and micro-dilution methods, the addition of CIN to ZEO during nanoemulsion formation (NZEOC) showed more antibacterial activity when compared to the individual addition of NZEO and CIN (NZEO+CIN). However, according to the vapor phase diffusion method, nano-treatments exhibited less inhibitory effects than the other treatments. Conclusion: It can be concluded that the fortification of essential oils with their derived pure compounds during nanoemulsion formation, can be used as a suitable alternative to chemical antibacterial compounds in the food industry.

Objective: The aim of the present study is to examine the phytochemical components and the biological activities of the whole parts of Onobrychis crista-galli (L.) Lam. growing in Algeria. Methods: The structures of the isolated compounds 1-15 were elucidated using different spectroscopic methods and by comparison with literature data. The biological evaluation of the plant was determined by the in vitro antioxidant and anti-inflammatory activities. The antioxidant activity of various extracts (petroleum ether, ethyl acetate, and n-butanol) and some isolated flavonoids was assessed by using five different test systems, namely, 1,1-diphenyl-2-picryl-hydrazil (DPPH), 2,2’- azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), cupric reducing antioxidant capacity (CUPRAC), superoxide alkaline DMSO, and β-carotene/linoleic acid tests. In addition, the total phenolic and flavonoid contents of the extracts were determined as gallic acid and quercetin equivalents, respectively. In vitro anti-inflammatory activity by protein denaturation was measured for all extracts. Results: Phytochemical investigation of the ethyl acetate and n-butanol extracts of Onobrychis crista- galli led to the isolation for the first time of fifteen known compounds. The present study reports for the first time the isolation and identification of fifteen known compounds from this species. The ethyl acetate extract had rich phenolic content indicating (31.09 ± 0.40 mg gallic acid equivalents/g of fresh weight), while n-butanol extract displayed a high content in flavonoid compounds (60.70±0.7 mg quercetin equivalents/ g of fresh weight). This investigation indicated that the ethyl acetate extract of O. crista-galli showed the highest antioxidant activity (IC50= 17.13±0.51 μg/mL, DPPH), (IC50= 82.99±2.50 μg/mL, ABTS), and (A0.50= 94.67±0.41 μg/mL, CUPRAC), (IC50= 97.09±2.20 μg/mL, DMSO), (IC50: 36.73±1.17 μg/mL, β-carotene/linoleic acid). Furthermore, the compound luteolin 5-methyl ether (14) exhibited a good antioxidant activity in DPPH (IC50= 06.05 ± 0.15 μg /mL) and CUPRAC (A0.5= 12.57 ± 0.34 μg /mL) assays. Moreover, the ethyl acetate and nbutanol extracts of O. crista-galli evidenced a good to moderate in vitro anti-inflammatory activity. Conclusion: The extracts of the whole plant of O. crista-galli (L.) Lam. showed potent antioxidant and anti-inflammatory activities.

Background: The therapeutic effects of a number of natural products on Inflammatory Bowel Disease (IBD) have recently been examined in detail. The whole herb and roots of Angelica keiskei (Umblliferae) have traditionally been used as a diuretic, to treat gastrointestinal diseases such as gastric ulcers and diarrhea in Japan. Objectives: The present study was performed to investigate the effects of xanthoangelol, a major chalcone of Angelica keiskei roots, on diarrhea and inflammation in the large intestine of IBD model mice. Methods: Xanthoangelol (10 & 25 mg/kg) was orally administered to mice with 3% Dextran Sulfate Sodium (DSS)-induced colitis. Blood samples were collected during the experimental period, subjected to a full blood count test, and colonic cytokine and chemokine levels were measured. Results: Xanthoangelol (25 mg/kg) reduced the Disease Activity Index (DAI) of colitis. It also attenuated DSS-induced reductions in red blood cell and platelet counts as well as Hb and Ht levels. A histological examination of the colon using direct fast scarlet staining showed that xanthoangelol prevented DSS-induced mucosal ulceration and eosinophil infiltration. Xanthoangelol also reduced DSS-induced increases in colonic MCP-1, IL-1β, and TNF-α levels. Conclusion: Xanthoangelol reduced DSS-induced increases in colonic IL-1β, TNF-α, and MCP-1 levels and prevented eosinophil infiltration, which supports its potential as a treatment for IBD.

Background: Although depression is the predominant phase in Bipolar Disorder (BPD) and causes the most psychosocial disability, optimal pharmacotherapy of bipolar depression is not known yet. Advances in research on BPD neurobiology have demonstrated that oxidative toxic stress (OTS) may be involved in the pathophysiology of BPD. Objective: The present study aimed to evaluate the effects of adjuvant CoQ10, supplement with potent antioxidant properties, on salivary and urinary OTS biomarkers in patients with BPD during the depressive episode. Material and Methods: 89 BPD patients with current depressive episode were allocated into either CoQ10 (200 mg/day) or placebo group by block randomization method. The salivary and urinary levels of OTS biomarkers including Total Antioxidant Capacity (TAC) and DNA damage were measured at baseline and 8 weeks after treatment. Results: At baseline, urinary and salivary levels of TAC and DNA damage were statistically comparable between the two groups. After 8 weeks treatment with CoQ10, patients showed significantly higher increment in urinary TAC level compared to placebo, while salivary level of TAC did not display significant differences between the two groups. Although changes in salivary and urinary DNA damage levels were greater in CoQ10 group, the changes reached significant level only in the urine sample. Conclusion: Our findings suggest that CoQ10 can improve OTS status in BPD patients during depressive episode. As activation of oxidative stress is one of the mechanisms responsible for BPD, it seems that CoQ10 due to its proven antioxidant properties, as add on therapy to standard treatment may be a promising agent in treating bipolar depression.