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Fulltext 4,5,4'-Trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin from Gynura segetum inhibit phagocytosis, lymphocyte proliferation, cytokine release and nitric oxide production from phagocytic cells

Yuandani, Jantan I, Husain K

BMC Complement Altern Med, 2017 Apr 11;17(1):211.
PMID: 28399868 DOI: 10.1186/s12906-017-1726-z

BACKGROUND: Gynura segetum is used traditionally to treat various ailments related to the immune system, which include cancer, inflammation, rheumatism, diabetes, hypertension, and viral infections but little studies have been carried out to validate their ethnopharmacological aspects. In this study the immunosuppressive effects of G. segetum and its constituents were investigated.
METHODS: Isolation of compounds from G. segetum leaves was conducted using vacuum liquid chromatography (VLC) and column chromatography (CC). Two new compounds, namely 4,5,4'-trihydroxychalcone and 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol, together with stigmasterol and β-sitosterol were isolated from G. segetum methanol extract and their structures were determined spectroscopically. The presence of gallic acid and rutin in the extract was determined quantitatively by a validated HPLC method. G. segetum methanol extract and its constituents were investigated for their effects on chemotaxis, phagocytosis, β2 integrin (CD18) expression, and reactive oxygen species (ROS) of polymorphonuclear leukocytes (PMNs), lymphocytes proliferation, cytokine release and nitric oxide (NO) production of phagocytes.
RESULTS: All the samples significantly inhibited all the innate immune responses tested except CD 18 expression on surface of leukocytes. Among the samples, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol exhibited the strongest inhibitory on chemotaxis, phagocytosis, ROS and NO production. The compound exhibited exceptionally strong inhibitions on ROS and chemotaxis activities with IC50 values lower than the positive controls, aspirin and ibuprofen, respectively. 4,5,4'-Trihydroxychalcone revealed the strongest immunosuppressive activity on proliferation of lymphocytes (IC50 value of 1.52 μM) and on release of IL-1β (IC50 value of 6.69 μM). Meanwhile rutin was the most potent sample against release of TNF-α from monocytes (IC50, 16.96 μM).
CONCLUSION: The extract showed strong immunosuppressive effects on various components of the immune system and these activities were possibly contributed mainly by 4,5,4'-trihydroxychalcone, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol and rutin.
An overview of structure-activity relationship studies of curcumin analogs as antioxidant and anti-inflammatory agents

Arshad L, Haque MA, Abbas Bukhari SN, Jantan I

Future Med Chem, 2017 04;9(6):605-626.
PMID: 28394628 DOI: 10.4155/fmc-2016-0223

Curcumin, extracted mainly from Curcuma longa rhizomes, has been reported to possess potent anti-inflammatory and anti-oxidant activities. Although safe at higher doses and exhibiting multiple biological activities, curcumin still has the problem of poor bioavailability which has been an attractive area of research over the last few years. A number of efforts have been made by modifying structural features of curcumin. This review highlights the structurally modified and more stable newly synthesized curcumin analogs that have been screened against antioxidant and anti-inflammatory activities. Also the structure-activity relationship to gain insight into future guidelines for scheming new compounds has been discussed, and further these analogs being more stable may serve as promising agents for use in different pathological conditions.
Tocotrienols Stimulate Insulin Secretion of Rat Pancreatic Isolated Islets in a Dynamic Culture

Chia LL, Jantan I, Chua KH

Curr Pharm Biotechnol, 2017;18(7):560-568.
PMID: 28786357 DOI: 10.2174/1389201018666170808144703

BACKGROUND: Tocotrienols (T3) are the naturally occurring vitamin E derivatives that possess antioxidant properties and therapeutic potential in diabetic complications. The bioactivities of the derivatives are determined by the number and arrangement of methyl substitution on the structure.
OBJECTIVE: The objective of this study was to determine the effects of T3 derivatives, σ-T3, γ-T3 and α-T3 on insulin secretion of rat pancreatic islets in a dynamic culture.
METHOD: Pancreatic islets isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation that provided a stable cell culture environment. Glucose (2.8 mM and 16.7 mM, as basal and stimulant, respectively) and potassium chloride (KCl) (30 mM) were added to the treatment in calcium free medium. The supernatant was collected for insulin measurements.
RESULTS: Short-term exposure (1 h) of σ-T3 to β cells in the stimulant glucose condition significantly potentiated insulin secretion in a dose-dependent manner. γ-T3 and α-T3 also displayed dosedependent effect but were less effective in the activation of insulin secretion. Essentially, KCl, a pancreatic β cell membrane depolarizing agent, added into the treatment further enhanced the insulin secretion of σ-T3, γ-T3 and α-T3 with ED50 values of 504, 511 and 588 µM, respectively.
CONCLUSION: The findings suggest the potential of σ-T3 in regulating glucose-stimulated insulin secretion (GSIS) in response to the intracellular calcium especially in the presence of KCl.
Fulltext Immunosuppressive Effects of Natural α,β-Unsaturated Carbonyl-Based Compounds, and Their Analogs and Derivatives, on Immune Cells: A Review

Arshad L, Jantan I, Bukhari SN, Haque MA

Front Pharmacol, 2017;8:22.
PMID: 28194110 DOI: 10.3389/fphar.2017.00022

The immune system is complex and pervasive as it functions to prevent or limit infections in the human body. In a healthy organism, the immune system and the redox balance of immune cells maintain homeostasis within the body. The failure to maintain the balance may lead to impaired immune response and either over activity or abnormally low activity of the immune cells resulting in autoimmune or immune deficiency diseases. Compounds containing α,β-unsaturated carbonyl-based moieties are often reactive. The reactivity of these groups is responsible for their diverse pharmacological activities, and the most important and widely studied include the natural compounds curcumin, chalcone, and zerumbone. Numerous studies have revealed the mainly immunosuppressive and anti-inflammatory activities of the aforesaid compounds. This review highlights the specific immunosuppressive effects of these natural α,β-unsaturated carbonyl-based compounds, and their analogs and derivatives on different types of immune cells of the innate (granulocytes, monocytes, macrophages, and dendritic cells) and adaptive (T cells, B cells, and natural killer cells) immune systems. The inhibitory effects of these compounds have been comprehensively studied on neutrophils, monocytes and macrophages but their effects on T cells, B cells, natural killer cells, and dendritic cells have not been well investigated. It is of paramount importance to continue generating experimental data on the mechanisms of action of α,β-unsaturated carbonyl-based compounds on immune cells to provide useful information for ensuing research to discover new immunomodulating agents.
Recent Updates on the Phytochemistry, Pharmacological, and Toxicological Activities of Zingiber zerumbet (L.) Roscoe ex Sm

Haque MA, Jantan I

Curr Pharm Biotechnol, 2017;18(9):696-720.
PMID: 29141544 DOI: 10.2174/1389201018666171115115458

BACKGROUND: Zingiber zerumbet (L.) Roscoe ex Sm. (family, Zingiberaceae) is a potent medicinal herb widely known as shampoo ginger and its rhizome is used in numerous ethnomedicinal applications including antipyretic, anti-inflammatory, antibacterial, anti-diarrheal, antidiabetics, carminative, and diuretic. The aim of this review was to bring together all the scientific updates on the phytochemistry and pharmacological activities of this herb, including their toxicological studies, and critically analyzed the outcomes to provide directions for future research on the herb as potential source of bioactive metabolites for pharmaceutical and nutraceutical applications.
METHODS: A structured electronic search on worldwide accepted scientific databases (Web of Science, PubMed, Google Scholar, Science Direct, SciFinder, Wiley Online Library) was carried out to compile the relevant information. Some information was obtained from books and database on medicinal plants used in various countries.
RESULTS: About 60 metabolites, mainly polyphenols, and terpenoids have been isolated and identified. However, most of the reported pharmacological studies were based on crude extracts, and only a few of those isolated metabolites, particularly zerumbone have been investigated for biological and pharmacological activities. Many of the mechanistic studies to understand the pharmacological effects of the plant are limited by many considerations with regard to design, experimentation and interpretation.
CONCLUSION: The bioactive metabolites should be further investigated on their safety and more elaborate preclinical studies before clinical trials can be undertaken.
Phyllanthin from Phyllanthus amarus inhibits cellular and humoral immune responses in Balb/C mice

Ilangkovan M, Jantan I, Bukhari SN

Phytomedicine, 2016 Nov 15;23(12):1441-1450.
PMID: 27765364 DOI: 10.1016/j.phymed.2016.08.002

BACKGROUND: Phyllanthin found in many Phyllanthus species has various biochemical and pharmacological properties especially on its hepatoprotective effects. However, its effect on the immune system has not been well documented.
PURPOSE: In the present study, phyllanthin isolated from Phyllanthus amarus was investigated for its immunosuppressive effects on various cellular and humoral immune responses in Balb/C mice.
METHODS: Male mice were treated daily at 20, 40 and 100mg/kg of phyllanthin for 14 days by oral gavage. The effects of phyllanthin on cellular immune responses in treated /non treated mice were determined by measuring CD 11b/CD 18 integrin expression, phagocytosis, nitric oxide (NO) production, myeloperoxidase activity (MPO), T and B cells proliferation, lymphocyte phenotyping, serum cytokines production by activated T-cells and delayed type hypersensitivity (DTH). Its effects on humoral immune responses were evaluated by determining the serum levels of lysozyme and ceruloplasmin, and immunoglobulins (IgG and IgM).
RESULTS: Phyllanthin dose-dependently inhibited CD11b/CD18 adhesion, the engulfment of E. coli by peritoneal macrophages molecules, NO and MPO release in treated mice. Phyllanthin caused significant and dose-dependent inhibition of T and B lymphocytes proliferation and down-regulation of the Th1 (IL-2 and IFN-γ) and Th2 (IL-4) cytokines. Phyllanthin at 100mg/kg caused a significant reduction in the percentage expression of CD4(+) and CD8(+) in splenocytes and the inhibition was comparable to that of cyclosporin A at 50mg/kg. At 100mg/kg, phyllanthin also dose-dependently exhibited strong inhibition on the sheep red blood cell (sRBC)-induced swelling rate of mice paw in DTH. Significant inhibition of serum levels of ceruloplasmin and lysozyme were observed in mice fed with higher doses (40 and 100mg/kg) of phyllanthin. Anti-sRBC immunoglobulins (IgM and IgG) antibody titer was down-regulated in immunized and phyllanthin-treated mice in a dose-dependent manner with maximum inhibition being observed at 100mg/kg.
CONCLUSION: The strong inhibitory effects of phyllanthin on the cellular and humoral immune responses suggest that phyllanthin may be a good candidate for development into an effective immunosuppressive agent.
Anti-inflammatory trends of new benzimidazole derivatives

Bukhari SN, Lauro G, Jantan I, Fei Chee C, Amjad MW, Bifulco G, et al.

Future Med Chem, 2016 Oct;8(16):1953-1967.
PMID: 27654499

In present study, the anti-inflammatory activities of a new series of benzimidazole derivatives were studied, investigating their inhibition of secretory phospholipase A2, lipoxygenase, COXs and lipopolysaccharide-induced secretion of TNF-α and IL-6 in mouse RAW264.7 macrophages.
Inhibitory Effects of the Standardized Extract of Phyllanthus amarus on Cellular and Humoral Immune Responses in Balb/C Mice

Ilangkovan M, Jantan I, Mesaik MA, Bukhari SN

Phytother Res, 2016 Aug;30(8):1330-8.
PMID: 27137750 DOI: 10.1002/ptr.5633

Phyllanthus amarus has been shown to have strong inhibitory effects on phagocytic activity of human neutrophils and on cellular immune responses in Wistar-Kyoto rats. In this study, we investigated the effects of daily treatment of standardized extract of P. amarus at 50, 100 and 200 mg/kg for 14 days in Balb/C mice by measuring the myeloperoxidase activity (MPO), nitric oxide (NO) release, macrophage phagocytosis, swelling of footpad in delayed type hypersensitivity (DTH), and serum immunoglobulins, ceruloplasmin and lysozyme levels. Qualitative and quantitative analyses of the extract using validated reversed-phase HPLC methods identified phyllanthin, hypophyllanthin, corilagin and geraniin as the biomarkers. Significant dose-dependent inhibitions of MPO activity and NO release were observed in treated mice. The extract also inhibited E. coli phagocytic capacity of peritoneal macrophages of treated mice and inhibited the sheep red blood cells (sRBC)-induced swelling rate of mice paw in the DTH. There was also a significant decrease in non-specific humoral immunity including ceruloplasmin and lysozyme levels in the extract-fed groups as well as the release of serum level immunoglobulins. The strong inhibitory effects of the extract on the cellular and humoral immune responses suggest the potential of the plant to be developed as an effective immunosuppressive agent. Copyright © 2016 John Wiley & Sons, Ltd.
Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

Leng J, Qin HL, Zhu K, Jantan I, Hussain MA, Sher M, et al.

Chem Biol Drug Des, 2016 Jul 19.
PMID: 27434226 DOI: 10.1111/cbdd.12822

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β-unsaturated carbonyl-based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β-induced cytotoxicity was also studied. Six compounds including 3f, 3o, 3u, 3ae, 3af, and 3ag were discovered to be most protective against Aβ-induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO-B, AChE, and self-induced Aβ1-42 aggregation. The compound 3f exhibited best AChE (IC50 = 0.045 ± 0.02 μm) inhibitory potential in addition to potent inhibition of MAO-B (IC50 = 0.88 ± 0.12 μm). Furthermore, compound 3f disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.
Effects of Labisia pumila var alata extracts on the lipid profile, serum antioxidant status and abdominal aorta of high-cholesterol diet rats

Dianita R, Jantan I, Jalil J, Amran AZ

Phytomedicine, 2016 Jul 15;23(8):810-7.
PMID: 27288916 DOI: 10.1016/j.phymed.2016.04.004

BACKGROUND: Previous studies on Labisia pumila var. alata (LPva) have showed that it could inhibit low-density lipoprotein (LDL) oxidation and provide protection on myocardial infarction in rats.
HYPOTHESIS/PURPOSE: We hypothesized that LPva extracts can modulate the lipid profiles and serum antioxidant status of hypercholesterolemic rats. In the present study, we investigated the effects of aqueous and 80% ethanol extracts of LPva on atherogenic and serum antioxidant parameters as well as changes in abdominal aorta of high-cholesterol diet rats.
METHODS: The major components of the extracts, gallic acid, flavonoids and alkyl resorcinols were analyzed by using a validated reversed phase HPLC method. The rats were induced to hypercholesterolemic status with daily intake of 2% cholesterol for a duration of 8 weeks. Three different doses (100, 200 and 400mg/kg) of the extracts were administered daily on the 4th week onwards. The rats were then sacrificed and the blood was collected via abdominal aorta and serum was separated by centrifugation for biochemical analysis. Part of the aorta tissues were excised immediately for histopathological examination.
RESULTS: The serum of LPva treated rats showed significant reduction in serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels and the abdominal aorta showed a significant decrease of atheroma lesions in treated rats. Serum lipid profiles of treated rats showed a decrease in total cholesterol, total triglycerides and low-density lipoprotein (LDL) levels as compared to control group. The atherogenic indices in treated rats were significantly improved along with an increasing level of serum high-density lipoprotein (HDL). The extracts also exhibited significant increase of antioxidant enzymes and decrease of MDA as a product of lipid peroxidation.
CONCLUSION: LPva extracts can reduce the risk of dyslipidemia by improving the serum lipid profiles and modulating serum antioxidants.
Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation

Zha GF, Zhang CP, Qin HL, Jantan I, Sher M, Amjad MW, et al.

Bioorg Med Chem, 2016 05 15;24(10):2352-9.
PMID: 27083471 DOI: 10.1016/j.bmc.2016.04.015

A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.
Synthesis of unsymmetrical monocarbonyl curcumin analogues with potent inhibition on prostaglandin E2 production in LPS-induced murine and human macrophages cell lines

Mohd Aluwi MF, Rullah K, Yamin BM, Leong SW, Abdul Bahari MN, Lim SJ, et al.

Bioorg Med Chem Lett, 2016 05 15;26(10):2531-8.
PMID: 27040659 DOI: 10.1016/j.bmcl.2016.03.092

The syntheses and bioactivities of symmetrical curcumin and its analogues have been the subject of interest by many medicinal chemists and pharmacologists over the years. To improve our understanding, we have synthesized a series of unsymmetrical monocarbonyl curcumin analogues and evaluated their effects on prostaglandin E2 production in lipopolysaccharide-induced RAW264.7 and U937 cells. Initially, compounds 8b and 8c exhibited strong inhibition on the production of PGE2 in both LPS-stimulated RAW264.7 (8b, IC50=12.01μM and 8c, IC50=4.86μM) and U937 (8b, IC50=3.44μM and 8c, IC50=1.65μM) cells. Placing vanillin at position Ar2 further improved the potency when both compounds 15a and 15b significantly lowered the PGE2 secretion level (RAW264.7: 15a, IC50=0.78μM and 15b, IC50=1.9μM while U937: 15a, IC50=0.95μM and 15b, IC50=0.92μM). Further experiment showed that compounds 8b, 8c, 15a and 15b did not target the activity of downstream inflammatory COX-2 mediator. Finally, docking simulation on protein targets COX-2, IKK-β, ERK, JNK2, p38α and p38β were performed using the conformation of 15a determined by single-crystal XRD.
Synthesis of α,β-Unsaturated Carbonyl-Based Compounds, Oxime and Oxime Ether Analogs as Potential Anticancer Agents for Overcoming Cancer Multidrug Resistance by Modulation of Efflux Pumps in Tumor Cells

Qin HL, Leng J, Zhang CP, Jantan I, Amjad MW, Sher M, et al.

J Med Chem, 2016 Apr 14;59(7):3549-61.
PMID: 27010345 DOI: 10.1021/acs.jmedchem.6b00276

Sixty-nine novel α,β-unsaturated carbonyl based compounds, including cyclohexanone, tetralone, oxime, and oxime ether analogs, were synthesized. The antiproliferative activity determined by using seven different human cancer cell lines provided a structure-activity relationship. Compound 8ag exhibited high antiproliferative activity against Panc-1, PaCa-2, A-549, and PC-3 cell lines, with IC50 value of 0.02 μM, comparable to the positive control Erlotinib. The ten most active antiproliferative compounds were assessed for mechanistic effects on BRAF(V600E), EGFR TK kinases, and tubulin polymerization, and were investigated in vitro to reverse efflux-mediated resistance developed by cancer cells. Compound 8af exhibited the most potent BRAF(V600E) inhibitory activity with an IC50 value of 0.9 μM. Oxime analog 7o displayed the most potent EGFR TK inhibitory activity with an IC50 of 0.07 μM, which was analogous to the positive control. Some analogs including 7f, 8af, and 8ag showed a dual role as anticancer and MDR reversal agents.
Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Ali-Seyed M, Jantan I, Vijayaraghavan K, Bukhari SN

Chem Biol Drug Des, 2016 Apr;87(4):517-36.
PMID: 26535952 DOI: 10.1111/cbdd.12682

An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.
Standardized extract of Tinospora crispa stimulates innate and adaptive immune responses in Balb/c mice

Ahmad W, Jantan I, Kumolosasi E, Bukhari SN

Food Funct, 2016 Mar 16;7(3):1380-9.
PMID: 26839149 DOI: 10.1039/c5fo01531f

Standardized extract of Tinospora crispa has been shown to exhibit immunostimulatory effects on innate immune responses in Wistar-Kyoto rats by enhancing neutrophil and T cell-mediated immunity. In this study the immunostimulatory effects of T. crispa were further investigated on the cellular immune response by determining its effect on nitric oxide (NO) production ability, peritoneal macrophage phagocytosis and delayed type hypersensitivity (DTH), whereas the humoral immune response was evaluated through the measurement of serum immunoglobulins (IgG and IgM) and serum lysozyme levels. Male Balb/c mice were immunized with 200 μL of 5 × 10(9) sheep red blood cells (sRBCs) per mL on day 0 and orally administered with 50, 100 and 200 mg per kg of ethanol extract of T. crispa for 14 days. Syringin and magnoflorine were qualitatively and quantitatively analyzed in the extract as chemical markers by using a validated reversed-phase high performance liquid chromatography method. T. crispa extract (TCE) considerably improved the peritoneal macrophages' ability to engulf FITC-labeled E. coli in a dose-dependent manner. TCE also dose-dependently promoted NO production in peritoneal macrophages activated by a lipopolysaccharide (LPS) and markedly potentiated the sRBS-induced swelling rate of the mice paw in DTH. The extract significantly enhanced the level of serum immunoglobulins, showing maximum activity at 100 mg kg(-1). Compared to the control groups, the serum lysozyme level and myeloperoxidase (MPO) activity were significantly higher in extract-treated groups. These findings suggest that T. crispa possesses strong immunostimulatory activities and might act as a natural immunomodulator as well as a potential nutraceutical for the modulation of the immune response.
Mimosa pudica L., a High-Value Medicinal Plant as a Source of Bioactives for Pharmaceuticals

Muhammad G, Hussain MA, Jantan I, Bukhari SNA

Compr Rev Food Sci Food Saf, 2016 Mar;15(2):303-315.
PMID: 33371596 DOI: 10.1111/1541-4337.12184

Mimosa pudica Linn. (Family: Mimosaceae) is used as an ornamental plant due to its thigmonastic and nyctinastic movements. M. pudica is also used to avoid or cure several disorders like cancer, diabetes, hepatitis, obesity, and urinary infections. M. pudica is famous for its anticancer alkaloid, mimosine, along with several valuable secondary metabolites like tannins, steroids, flavonoids, triterpenes, and glycosylflavones. A wide array of pharmacological properties like antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, antinociceptive, anticonvulsant, antidepressant, antidiarrheal, hypolipidemic activities, diuretic, antiparasitic, antimalarial, and hypoglycemic have been attributed to different parts of M. pudica. Glucuronoxylan polysaccharide extruded from seeds of M. pudica is used for drug release formulations due to its high swelling index. This review covers a thorough examination of functional bioactives as well as pharmacological and phytomedicinal attributes of the plant with the purpose of exploring its pharmaceutical and nutraceutical potentials.
A Comprehensive Review on the Chemotherapeutic Potential of Piceatannol for Cancer Treatment, with Mechanistic Insights

Seyed MA, Jantan I, Bukhari SN, Vijayaraghavan K

J Agric Food Chem, 2016 Feb 3;64(4):725-37.
PMID: 26758628 DOI: 10.1021/acs.jafc.5b05993

Cancer is a diverse class of diseases characterized by uncontrolled cell growth that constitutes the greatest cause of mortality and morbidity worldwide. Despite steady progress, the treatment modalities of cancer are still insufficient. Several new concepts have emerged for therapeutic intervention in malignant diseases with the goal of identifying specific targets and overcoming resistance against current cytotoxic therapies. Many studies have reported the remarkable and significant properties of dietary plant polyphenols such as curcumin, resveratrol, flavopiridol, indirubin, magnolol, piceatannol, parthenolide, epigallocatechin gallate, and cucurbitacin as anticancer agents known for their pleiotropic effects on cancer, immune cells, and inflammation. Piceatannol, an analogue and metabolite of resveratrol, is a natural stilbene commonly found in grape skins and wine. Compared to resveratrol, this molecule exhibits superior bioactivities as an inhibitor of COX-1/2 and the CSN-associated kinase. Piceatannol is thought to be a potent natural compound with many therapeutic effects, such as the prevention of hypercholesterolemia, arrhythmia, atherosclerosis, angiogenesis, and cardiovascular diseases. It also demonstrates vasorelaxation, antioxidant, and anticancer activities. This comprehensive review summarizes the current data regarding the mechanisms of action of piceatannol, its chemopreventive properties, and its possible therapeutic potential against various types of human cancer.
Fulltext Isolation of Terpenoids from the Stem of Ficus aurantiaca Griff and their Effects on Reactive Oxygen Species Production and Chemotactic Activity of Neutrophils

Mawa S, Jantan I, Husain K

Molecules, 2016 Jan 05;21(1):9.
PMID: 26742027 DOI: 10.3390/molecules21010009

Three new triterpenoids; namely 28,28,30-trihydroxylupeol (1); 3,21,21,26-tetrahydroxy-lanostanoic acid (2) and dehydroxybetulinic acid (3) and seven known compounds; i.e., taraxerone (4); taraxerol (5); ethyl palmitate (6); herniarin (7); stigmasterol (8); ursolic acid (9) and acetyl ursolic acid (10) were isolated from the stem of Ficus aurantiaca Griff. The structures of the compounds were established by spectroscopic techniques. The compounds were evaluated for their inhibitory effects on polymorphonuclear leukocyte (PMN) chemotaxis by using the Boyden chamber technique and on human whole blood and neutrophil reactive oxygen species (ROS) production by using a luminol-based chemiluminescence assay. Among the compounds tested, compounds 1-4, 6 and 9 exhibited strong inhibition of PMN migration towards the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) with IC50 values of 6.8; 2.8; 2.5; 4.1; 3.7 and 3.6 μM, respectively, comparable to that of the positive control ibuprofen (6.7 μM). Compounds 2-4, 6, 7 and 9 exhibited strong inhibition of ROS production of PMNs with IC50 values of 0.9; 0.9; 1.3; 1.1; 0.5 and 0.8 μM, respectively, which were lower than that of aspirin (9.4 μM). The bioactive compounds might be potential lead molecules for the development of new immunomodulatory agents to modulate the innate immune response of phagocytes.
Fulltext Tinospora crispa (L.) Hook. f. & Thomson: A Review of Its Ethnobotanical, Phytochemical, and Pharmacological Aspects

Ahmad W, Jantan I, Bukhari SN

Front Pharmacol, 2016;7:59.
PMID: 27047378 DOI: 10.3389/fphar.2016.00059

Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae), found in the rainforests or mixed deciduous forests in Asia and Africa, is used in traditional medicines to treat numerous health conditions. This review summarizes the up-to-date reports about the ethnobotany, phytochemistry, pharmacological activities, toxicology, and clinical trials of the plant. It also provides critical assessment about the present knowledge of the plant which could contribute toward improving its prospect as a source of lead molecules for drug discovery. The plant has been used traditionally in the treatment of jaundice, rheumatism, urinary disorders, fever, malaria, diabetes, internal inflammation, fracture, scabies, hypertension, reducing thirst, increasing appetite, cooling down the body temperature, and maintaining good health. Phytochemical analyses of T. crispa revealed the presence of alkaloids, flavonoids, and flavone glycosides, triterpenes, diterpenes and diterpene glycosides, cis clerodane-type furanoditerpenoids, lactones, sterols, lignans, and nucleosides. Studies showed that the crude extracts and isolated compounds of T. crispa possessed a broad range of pharmacological activities such as anti-inflammatory, antioxidant, immunomodulatory, cytotoxic, antimalarial, cardioprotective, and anti-diabetic activities. Most pharmacological studies were based on crude extracts of the plant and the bioactive compounds responsible for the bioactivities have not been well identified. Further investigations are required to transform the experience-based claims on the use of T. crispa in traditional medicine practices into evidence-based information. The plant extract used in pharmacological and biological studies should be qualitatively and quantitatively analyzed based on its biomarkers. There should be detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more elaborate toxicity study to ensure safety of the plant for human use. More clinical trials are encouraged to be carried out if there are sufficient preclinical and safety data.
Fulltext Inhibitory effects of compounds from Phyllanthus amarus on nitric oxide production, lymphocyte proliferation, and cytokine release from phagocytes

Yuandani, Jantan I, Ilangkovan M, Husain K, Chan KM

Drug Des Devel Ther, 2016;10:1935-45.
PMID: 27354767 DOI: 10.2147/DDDT.S105651

Standardized extract of Phyllanthus amarus has previously been shown to have a strong inhibitory effect on phagocytic activity of human neutrophils. The current study was carried out to evaluate the effects of constituents of the extract of P. amarus on nitric oxide (NO) production as well as lymphocyte proliferation and cytokine release from phagocytes. Three compounds, ethyl 8-hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene, and 1,7,8-trihydroxy-2-naphtaldehyde, together with seven known compounds were isolated from the whole plant of P. amarus. The isolated compounds and reference standards, ie, gallic acid, ellagic acid, corilagin, and geraniin, which were quantitatively analyzed in the extracts, were evaluated for their effects on immune cells. Among the compounds tested, the lignans, especially phyltetralin and phyllanthin, showed strong inhibition on lymphocyte proliferation with half maximal inhibitory concentration (IC50) values of 1.07 μM and 1.82 μM, respectively. Ethyl 8-hydroxy-8-methyl-tridecanoate and 1,7,8-trihydroxy-2-naphtaldehyde exhibited strong inhibition on nitric oxide production with IC50 values of 0.91 μM and 1.07 μM, respectively. Of all the compounds, corilagin was the strongest inhibitor of tumor necrosis factor-α release with an IC50 value of 7.39 μM, whereas geraniin depicted the strongest inhibitory activity on interleukin-1β release with an IC50 value of 16.41 μM. The compounds constituting the extract of P. amarus were able to inhibit the innate immune response of phagocytes at different steps.

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