Displaying publications 1 - 20 of 50 in total

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  1. Yuandani, Jantan I, Haque MA, Rohani AS, Nugraha SE, Salim E, et al.
    Front Pharmacol, 2023;14:1222195.
    PMID: 37533631 DOI: 10.3389/fphar.2023.1222195
    Zingiber and Alpinia species (family: Zingiberaceae) are popularly used in food as spices and flavoring agents and in ethnomedicine to heal numerous diseases, including immune-related disorders. However, their ethnomedicinal uses have not been sufficiently supported by scientific investigations. Numerous studies on the modulating effects of plants and their bioactive compounds on the different steps of the immune system have been documented. This review aimed to highlight up-to-date research findings and critically analyze the modulatory effects and mechanisms of the extracts and secondary compounds of several Zingiber and Alpinia species, namely, Zingiber officinale Roscoe, Z. cassumunar Roxb., Z. zerumbet (L.) Roscoe ex Sm., Alpinia galanga Linn., A. conchigera Griff, A. katsumadai Hayata, A. oxyphylla Miq., A. officinarum Hance, A. zerumbet (Pers.) Burtt. et Smith, and A. purpurata (Viell.) K. Schum. on the immune system, particularly via the inflammation-related signaling pathways. The immunomodulating activities of the crude extracts of the plants have been reported, but the constituents contributing to the activities have mostly not been identified. Among the extracts, Z. officinale extracts were the most investigated for their in vitro, in vivo, and clinical effects on the immune system. Among the bioactive metabolites, 6-, 8-, and 10-gingerols, 6-shogaol, and zerumbone from Zingiber species and cardamomin, 1'-acetoxychavicol acetate, yakuchinone, rutin, 1,8-cineole, and lectin from Alpinia species have demonstrated strong immunomodulating effects. More experimental studies using cell and animal models of immune-related disorders are necessary to further understand the underlying mechanisms, together with elaborate preclinical pharmacokinetics, pharmacodynamics, bioavailability, and toxicity studies. Many of these extracts and secondary metabolites are potential candidates for clinical development in immunomodulating agents or functional foods to prevent and treat chronic inflammatory disorders.
  2. Rahman MM, Ferdous KU, Roy S, Nitul IA, Mamun F, Hossain MH, et al.
    Food Sci Nutr, 2020 Jul;8(7):3578-3589.
    PMID: 32724620 DOI: 10.1002/fsn3.1640
    Amla (Emblica officinalis Gaertn.) is a natural source of antioxidants and possesses valuable medicinal properties. However, the protective effect of amla in the kidney of two-kidneys-one-clip (2K1C) rats has not been explained sufficiently. This study was performed to evaluate the renoprotective effect of amla fruit powder (2.5% W/W) supplementation in kidneys of 2K1C rats. 2K1C rats increased the remnant kidney wet weight and also increased plasma creatinine and uric acid concentration compared to the control. Amla supplementation ameliorates elevated creatinine and uric acid concentration in plasma of 2K1C rats. Various oxidative stress indicators such as malondialdehyde, nitric oxide (NO), and advanced protein oxidation product (APOP) were also increased in plasma, heart, and kidney tissues in 2K1C rats that were also significantly brought down to normal level by amla supplementation. Moreover, the inflammatory cells entry and fibrosis in the 2K1C rat's tissues were prevented by amla supplementation. These research results suggest that amla may restore plasma antioxidant capacities and prevents oxidative stress, inflammation, and fibrosis in 2K1C rats. Taken these results as a base, clinical supplementation of dried amla powder in diet or juice to the CKD patients would be beneficial.
  3. Rahaman I, Haque MA, Singh NSS, Jafor MS, Sarkar PK, Rahman MA, et al.
    Micromachines (Basel), 2022 Nov 11;13(11).
    PMID: 36422388 DOI: 10.3390/mi13111959
    In this research, a novel antenna array named Linearly arranged Concentric Circular Antenna Array (LCCAA) is proposed, concerning lower beamwidth, lower sidelobe level, sharp ability to detect false signals, and impressive SINR performance. The performance of the proposed LCCAA beamformer is compared with geometrically identical existing beamformers using the conventional technique where the LCCAA beamformer shows the lowest beamwidth and sidelobe level (SLL) of 12.50° and -15.17 dB with equal elements accordingly. However, the performance is degraded due to look direction error, for which robust techniques, fixed diagonal loading (FDL), optimal diagonal loading (ODL), and variable diagonal loading (VDL), are applied to all the potential arrays to minimize this problem. Furthermore, the LCCAA beamformer is further simulated to reduce the sidelobe applying tapering techniques where the Hamming window shows the best performance having 17.097 dB less sidelobe level compared to the uniform window. The proposed structure is also analyzed under a robust tapered (VDL-Hamming) method which reduces around 69.92 dB and 48.39 dB more sidelobe level compared to conventional and robust techniques. Analyzing all the performances, it is clear that the proposed LCCAA beamformer is superior and provides the best performance with the proposed robust tapered (VDL-Hamming) technique.
  4. Nuruzzaman M, Sharoni AM, Satoh K, Karim MR, Harikrishna JA, Shimizu T, et al.
    Front Plant Sci, 2015;6:676.
    PMID: 26442000 DOI: 10.3389/fpls.2015.00676
    Expression levels of the NAC gene family were studied in rice infected with Rice dwarf virus (RDV), Rice black-streaked dwarf virus (RBSDV), Rice grassy stunt virus (RGSV), Rice ragged stunt virus (RRSV), and Rice transitory yellowing virus (RTYV). Microarray analysis showed that 75 (68%) OsNAC genes were differentially regulated during infection with RDV, RBSDV, RGSV, and RRSV compared with the control. The number of OsNAC genes up-regulated was highest during RGSV infection, while the lowest number was found during RTYV infection. These phenomena correlate with the severity of the syndromes induced by the virus infections. Most of the genes in the NAC subgroups NAC22, SND, ONAC2, ANAC34, and ONAC3 were down-regulated for all virus infections. These OsNAC genes might be related to the health stage maintenance of the host plants. Interestingly, most of the genes in the subgroups TIP and SNAC were more highly expressed during RBSDV and RGSV infections. These results suggested that OsNAC genes might be related to the responses induced by the virus infection. All of the genes assigned to the TIP subgroups were highly expressed during RGSV infection when compared with the control. For RDV infection, the number of activated genes was greatest during infection with the S-strain, followed by the D84-strain and the O-strain, with seven OsNAC genes up-regulated during infection by all three strains. The Os12g03050 and Os11g05614 genes showed higher expression during infection with four of the five viruses, and Os11g03310, Os11g03370, and Os07g37920 genes showed high expression during at least three viral infections. We identified some duplicate genes that are classified as neofunctional and subfunctional according to their expression levels in different viral infections. A number of putative cis-elements were identified, which may help to clarify the function of these key genes in network pathways.
  5. Nisa FY, Rahman MA, Hossen MA, Khan MF, Khan MAN, Majid M, et al.
    Ann Med, 2021 Dec;53(1):1476-1501.
    PMID: 34433343 DOI: 10.1080/07853890.2021.1966088
    Alzheimer's disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis.Key messagesInevitable cascade mechanisms of how Alzheimer's Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed.Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited.Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.
  6. Mozumder MK, Jasmine UH, Haque MA, Haque S
    PLoS One, 2023;18(8):e0289597.
    PMID: 37582101 DOI: 10.1371/journal.pone.0289597
    BACKGROUND: Homosexual individuals are at high risk of suicide, but there is a shortage of data from developing countries to confirm this. Estimates on mental health and suicide risk among male homosexuals in Bangladesh are needed to generate awareness and to plan services accordingly.

    METHOD: We assessed mental health and suicidal behavior of 102 self-identified homosexual males from a community-based organization that works with the sexual minority population.

    RESULTS: One-third of the participants (32.4%) had experienced attempted suicide, and almost half (47.1%) had a history of suicidal ideation and self-harm (40.2%). Compared to a heterosexual sample, homosexual males had poorer mental health as they scored higher on Beck Hopelessness Scale (Cohen's d = 0.29) and General Health Questionnaire (GHQ) (Cohen's d = 0.57). The results revealed positive correlations between self-harm, suicidal ideation and suicide attempt scores. Participants with history of suicide attempt, suicide ideation and self-harm reported worse general health, more social dysfunction, and severe depression than those without such history.

    CONCLUSION: Suicidality and mental health conditions among homosexual males in Bangladesh have appeared to be alarming. Given the concerns, we offer some recommendations for practitioners and social workers who are serving this population in Bangladesh.

  7. Mohamed SIA, Jantan I, Haque MA
    Int Immunopharmacol, 2017 Sep;50:291-304.
    PMID: 28734166 DOI: 10.1016/j.intimp.2017.07.010
    Natural products with immunomodulatory activity are widely used in treatment of many diseases including autoimmune diseases, inflammatory disorders in addition to cancer. They gained a great interest in the last decades as therapeutic agents since they provide inexpensive and less toxic products than the synthetic chemotherapeutic agents. Immunomodulators are the agents that have the ability to boost or suppress the host defense response that can be used as a prophylaxis as well as in combination with other therapeutic modalities. The anticancer activity of these immunomodulators is due to their anti-inflammatory, antioxidant, and induction of apoptosis, anti-angiogenesis, and anti-metastasis effect. These natural immunomodulators such as genistein, curcumin, and resveratrol can be used as prophylaxis against the initiation of cancer besides the inhibition of tumor growth and proliferation. Whereas, immunostimulants can elicit and activate humoral and cell-mediated immune responses against the tumor that facilitate the recognition and destruction of the already existing tumor. This review represents the recent studies on various natural immunomodulators with antitumor effects. We have focused on the relationship between their anticancer activity and immunomodulatory mechanisms. The mechanisms of action of various immunomodulators such as polyphenolic compounds, flavonoids, organosulfur compounds, capsaicin, vinca alkaloids, bromelain, betulinic acid and zerumbone, the affected cancerous cell lines in addition to the targeted molecules and transcriptional pathways have been review and critically analyzed.
  8. Khandokar L, Bari MS, Seidel V, Haque MA
    J Ethnopharmacol, 2021 Oct 05;278:114313.
    PMID: 34116186 DOI: 10.1016/j.jep.2021.114313
    ETHNOPHARMACOLOGICAL RELEVANCE: Glycosmis pentaphylla (Retz.) DC. is a perennial shrub indigenous to the tropical and subtropical regions of India, China, Sri Lanka, Myanmar, Bangladesh, Indonesia, Malaysia, Thailand, Vietnam, Philippine, Java, Sumatra, Borneo and Australia. The plant is used extensively within these regions as a traditional medicine for the treatment of a variety of ailments including cough, fever, chest pain, anemia, jaundice, liver disorders, inflammation, bronchitis, rheumatism, urinary tract infections, pain, bone fractures, toothache, gonorrhea, diabetes, cancer and other chronic diseases.

    AIM OF THE REVIEW: This review aims to present up-to-date information regarding the taxonomy, botany, distribution, ethnomedicinal uses, phytochemistry, pharmacology and toxicological profile of G. pentaphylla. The presented information was analyzed critically to understand current work undertaken on this species and explore possible future prospects for this plant in pharmaceutical research.

    MATERIALS & METHODS: Bibliographic databases, including Google Scholar, PubMed, Web of Science, ScienceDirect, SpringerLink, Wiley Online Library, Semantic Scholar, Europe PMC, Scopus, and MEDLINE, were explored thoroughly for the collection of relevant information. The structures of phytoconstituents were confirmed with PubChem and SciFinder databases. Taxonomical information on the plant was presented in accordance with The Plant List (version 1.1).

    RESULTS: Extensive phytochemical investigations into different parts of G. pentaphylla have revealed the presence of at least 354 secondary metabolites belonging to structurally diverse classes including alkaloids, amides, phenolic compounds, flavonoids, glycosides, aromatic compounds, steroids, terpenoids, and fatty derivatives. A large number of in vitro and in vivo experiments have demonstrated that G. pentaphylla had anticancer, antimutagenic, antibacterial, antifungal, anthelmintic, mosquitocidal, antidiabetic, antihyperlipidemic, anti-oxidant, anti-inflammatory, analgesic, antipyretic, anti-arsenicosis, and wound healing properties. Toxicological studies have established the absence of any significant adverse reactions and showed that the plant had a moderate safety profile.

    CONCLUSIONS: G. pentaphylla can be suggested as a source of inspiration for the development of novel drugs, especially anticancer, antimicrobial, anthelmintic, and mosquitocidal agents. Moreover, bioassay-guided investigations into its diverse classes of secondary metabolites, especially the large pool of nitrogen-containing alkaloids and amides, promises the development of novel drug candidates. Future pharmacological studies into this species are also warranted as many of its traditional uses are yet to be validated scientifically.

  9. Jantan I, Haque MA, Ilangkovan M, Arshad L
    Int Immunopharmacol, 2019 Aug;73:552-559.
    PMID: 31177081 DOI: 10.1016/j.intimp.2019.05.035
    Zerumbone exhibited various biological properties including in vitro immunosuppressive effects. However, its modulatory activity on the immune responses in experimental animal model is largely unknown. This investigation was conducted to explore the effects of daily treatment of zerumbone (25, 50, and 100 mg/kg) isolated from Zingiber zerumbet rhizomes for 14 days on various cellular and humoral immune responses in Balb/C mice. For measurement of adaptive immunity, sheep red blood cells (sRBC) were used to immunize the mice on day 0 and orally fed with similar doses of zerumbone for 14 days. The effects of zerumbone on phagocytosis, nitric oxide (NO) release, myeloperoxidase (MPO) activity, proliferation of T and B cells, lymphocyte phenotyping, cytokines release in serum by activated T cells, delayed type hypersensitivity (DTH) and immunoglobulins production (IgG and IgM) were investigated. Zerumbone downregulated the engulfment of E. coli by peritoneal macrophages and the release of NO and MPO in a concentration-dependent manner. Zerumbone showed significant and concentration-dependent suppression of T and B lymphocytes proliferation and inhibition of the Th1 and Th2 cytokines release. At higher concentrations of zerumbone, the % expression of CD4+ and CD8+ in splenocytes was significantly inhibited. Zerumbone also concentration-dependently demonstrated strong suppression on sRBC-triggered swelling of mice paw in DTH. Substantial suppression of anti-sRBC immunoglobulins antibody titer was noted in immunized and zerumbone-treated mice in a concentration-dependent manner. The potent suppressive effects of zerumbone on the immune responses suggest that zerumbone can be a potential candidate for development of immunosuppressive agent.
  10. Jantan I, Haque MA, Arshad L, Harikrishnan H, Septama AW, Mohamed-Hussein ZA
    J Nutr Biochem, 2021 07;93:108634.
    PMID: 33794330 DOI: 10.1016/j.jnutbio.2021.108634
    The high failure rate of the reductionist approach to discover effective and safe drugs to treat chronic inflammatory diseases has led scientists to seek alternative ways. Recently, targeting cell signaling pathways has been utilized as an innovative approach to discover drug leads from natural products. Cell signaling mechanisms have been identified playing key role in diverse diseases by inducing proliferation, cell survival and apoptosis. Phytochemicals are known to be able to modulate the cellular and molecular networks which are associated to chronic diseases including cancer-associated inflammation. In this review, the roles of dietary polyphenols (apigenin, kaempferol, quercetin, curcumin, genistein, isoliquiritigenin, resveratrol and gallic acid) in modulating multiple inflammation-associated cell signaling networks are deliberated. Scientific databases on suppressive effects of the polyphenols on chronic inflammation via modulation of the pathways especially in the recent five years are gathered and critically analyzed. The polyphenols are able to modulate several inflammation-associated cell signaling pathways, namely nuclear factor-kappa β, mitogen activated protein kinases, Wnt/β-catenin and phosphatidylinositol 3-kinase and protein kinase B via selective actions on various components of the networks. The suppressive effects of the polyphenols on the multiple cell signaling pathways reveal their potential use in prevention and treatment of chronic inflammatory disorders. Understanding the mechanistic effects involved in modulation of the signaling pathways by the polyphenols is necessary for lead identification and development of future functional foods for prevention and treatment of chronic inflammatory diseases.
  11. Jantan I, Arshad L, Septama AW, Haque MA, Mohamed-Hussein ZA, Govender NT
    Phytother Res, 2023 Mar;37(3):1036-1056.
    PMID: 36343627 DOI: 10.1002/ptr.7671
    The worldwide spreading of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed a serious threat to health, economic, environmental, and social aspects of human lives. Currently, there are no approved treatments that can effectively block the virus although several existing antimalarial and antiviral agents have been repurposed and allowed use during the pandemic under the emergency use authorization (EUA) status. This review gives an updated overview of the antiviral effects of phytochemicals including alkaloids, flavonoids, and terpenoids against the COVID-19 virus and their mechanisms of action. Search for natural lead molecules against SARS-CoV-2 has been focusing on virtual screening and in vitro studies on phytochemicals that have shown great promise against other coronaviruses such as SARS-CoV. Until now, there is limited data on in vivo investigations to examine the antiviral activity of plants in SARS-CoV-2-infected animal models and the studies were performed using crude extracts. Further experimental and preclinical investigations on the in vivo effects of phytochemicals have to be performed to provide sufficient efficacy and safety data before clinical studies can be performed to develop them into COVID-19 drugs. Phytochemicals are potential sources of new chemical leads for the development of safe and potent anti-SARS-CoV-2 agents.
  12. Jantan I, Haque MA, Ilangkovan M, Arshad L
    Front Pharmacol, 2019;10:878.
    PMID: 31440162 DOI: 10.3389/fphar.2019.00878
    Phyllanthus species (family; Euphorbiaceae) have been intensively studied for their immunomodulating effects due to their wide-ranging uses to treat immune-related diseases in indigenous medicine, which are primarily lack of scientific basis. The focuses of this review are on the significance of Phyllanthus species and their bioactive metabolites particularly corilagin (1), geraniin (2), gallic acid (3), phyllanthin (4), hypophyllanthin (5), ellagic acid (6), phyltetralin (7), niranthin (8), catechin (9), quercetin (10), astragalin (11), and chebulagic acid (12) in the modulation of both innate and adaptive immune systems through various mechanisms and their possible therapeutic benefits for treatment of immune-related diseases. We have compiled all significant findings published in the literature, and the data were analyzed critically to provide perspectives and directions for future research for the plants as a prospective source of novel immunomodulating agents. Various Phyllanthus species particularly Phyllanthus amarus, Phyllanthus emblica, Phyllanthus niruri, and Phyllanthus urinaria have been documented to possess significant immunomodulatory effects. However, the possible challenges encountered by the application of extracts of various Phyllanthus species and their bioactive constituents as immunomodulators need to be addressed. Most reports on the biological and pharmacological studies of the plants were based on crude extracts. The extracts were not chemically characterized, and the contributions of their chemical constituents to the bioactivities were not identified. The underlying mechanisms involved in the immunomodulatory effects of the Phyllanthus species were not indepthly studied due to limitations in terms of design, conduct, and interpretation. Extensive experimental and preclinical studies on the immunomodulating potential of Phyllanthus species should be carried out to provide sufficient data to prove that their traditional uses are inherently effective and safe and will allow clinical trials to be pursued for their further development as therapeutic agents to treat immune-related disorders.
  13. Jantan I, Norahmad NA, Yuandani, Haque MA, Mohamed-Hussein ZA, Mohd Abd Razak MR, et al.
    PMID: 38619217 DOI: 10.1080/10408398.2024.2341266
    Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.
  14. Iqbal Chowdhury I, Rahman MA, Hashem MA, Bhuiyan MMH, Hajjar D, Alelwani W, et al.
    Animal Model Exp Med, 2020 Jun;3(2):140-151.
    PMID: 32613173 DOI: 10.1002/ame2.12115
    BACKGROUND: Justicia adhatoda and Ocimum tenuiflorum, locally known as bashok and tulsi, are two ethnomedicinally important herbs that have been using as dietary supplements for several therapeutic applications. This study evaluated the combined effect of both the herbs as an antioxidative and antihyperlipidemic agent.

    METHODS: Antihyperlipidemic effect was assessed in a high-fat diet-induced hyperlipidemic model in Wistar albino rats. The rats were treated orally with extracts of bashok (J adhatoda, 200 mg/kg bw), tulshi (O tenuiflorum, 200 mg/kg bw), and a combination of bashok and tulshi (50:50), as well as with a reference drug, atorvastatin (10 mg/kg/day), with or without high-fat diet for 14 days. The antioxidative effect was studied using established in vitro models. The studies were supported by experimentally testing the effects of the extracts on membrane stabilization and inhibition of protein denaturation.

    RESULTS: The results showed that the serum lipid profile was significantly decreased in the different treatment groups, with bashok having the greatest effect. Body weights, total serum protein, LDH, and relative liver and adipose tissue weights were markedly restored towards baseline values, the lowest atherogenic index being achieved with the combined extract. The combination treatment significantly enhanced total phenolic content and antioxidative capacity and greatly potentiated membrane stabilization, but inhibition of protein denaturation was not significantly affected.

    CONCLUSION: The data demonstrate that a combination of Justicia adhatoda and Ocimum tenuiflorum could be developed as a food supplement with antioxidative and antihyperlipidemic benefits.

  15. Hossen MA, Reza ASMA, Ahmed AMA, Islam MK, Jahan I, Hossain R, et al.
    Biomed Pharmacother, 2021 Mar;135:111211.
    PMID: 33421733 DOI: 10.1016/j.biopha.2020.111211
    Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p 
  16. Hossen MA, Ali Reza ASM, Amin MB, Nasrin MS, Khan TA, Rajib MHR, et al.
    Food Sci Nutr, 2021 Jul;9(7):3836-3851.
    PMID: 34262741 DOI: 10.1002/fsn3.2362
    Blumea lacera is an edible plant with imperative medicinal values. However, the anxiolytic and antidepressant roles of B. lacera have not been well-explained. Therefore, the current study aims to explore the impending bioactive metabolites and roles of B. lacera methanol leaf extract (Me-BLL) in attenuating anxiety and depression through several experimental and computer-aided approaches. The chemical characterization of Me-BLL was performed through standard phytochemical and GC-MS analyses. To explore the neuropharmacological insights, Swiss albino mice were treated with Me-BLL at doses of 200-400 mg/kg, p.o. The anxiolytic effects were observed employing elevated plus maze (EPM), light-dark box (LDB), and hole-board (HBT) tests, while antidepressant effects were evaluated using forced swimming (FST) and tail suspension tests (TST). Diazepam (1 mg/kg, i.p.) and fluoxetine HCl (20 mg/kg, p.o.) were used as the reference standard. The phytochemical analyses revealed several bioactive metabolites, including higher contents of total phenolics and flavonoids. The EPM and LDB tests demonstrated an increased time spent in open arms and light box, and the HBT showed an increased number of head dipping, indicating the anxiolytic effects of Me-BLL. The TST and FST revealed a decrease in immobility time, meaning the persuasive antidepressant effects. The antioxidative effects of Me-BLL have also been observed prominently. Correspondingly, the computer-aided investigation confirmed several bioactive lead molecules. Specifically, thymol and cuminol revealed potential anxiolytic and antioxidant effects, while stigmast-5-en-3.beta.-ol and gamma-sitosterol possessed promising antidepressant effects. Taken these results as a base, the plant has imperative potentials in managing anxiety and depression-like disorders.
  17. Hoque MA, Ahmad S, Chakrabarty N, Khan MF, Hafez Kabir MS, Brishti A, et al.
    Heliyon, 2021 Oct;7(10):e08199.
    PMID: 34729435 DOI: 10.1016/j.heliyon.2021.e08199
    Palm grass (Curculigo recurvata) is an ethnomedicinally important herb reported to have significant medicinal values. The present study aimed to evaluate the antidepressant and anxiolytic activities of a methanol extract of C. recurvata rhizome (Me-RCR) through different approaches. The antidepressant and anxiolytic properties of Me-RCR were assessed by using elevated plus maze (EPM), hole-board (HBT), tail suspension (TST), and forced swimming (FST) tests in Swiss Albino mice. The in-depth antioxidative potential of Me-RCR was also evaluated through DPPH radical scavenging activity, ferric-reducing power capacity, total phenolic, flavonoid, flavonol, and antioxidant content analysis. Computational investigations were performed using computer-aided methods for screening the anxiolytic, antidepressant, and antioxidative activities of the selected lead molecules. Treatment with Me-RCR (200 and 400 mg/kg, b.w.) notably increased the number of open arm entries and the time spent in the EPM test. In the HBT, Me-RCR exhibited significant anxiolytic activity at a dose of 200 mg/kg, whereas similar activity was observed at 400 mg/kg in the EPM test. Me-RCR significantly decreased the immobility time in a dose-dependent manner in both TST and FST. The IC50 for DPPH and reducing power capacity assay were found to be 18.56 and 193 μg/mL, respectively. Promising outcomes were noted for the determination of total phenolics, flavonoids, flavonols, and antioxidant capacity. In the case of computer-aided studies, nyasicoside showed promising binding energy for antidepressant and anxiolytic activities, whereas isocurculigine demonstrated promising effects as an antioxidant. Overall, these findings suggest that Me-RCR could be a favourable therapeutic candidate for the treatment of mental and psychiatric disorders, as well as a good source of antioxidants.
  18. Harikrishnan H, Jantan I, Haque MA, Kumolosasi E
    BMC Complement Altern Med, 2018 Jul 25;18(1):224.
    PMID: 30045725 DOI: 10.1186/s12906-018-2289-3
    BACKGROUND: Phyllanthus amarus has been used widely in various traditional medicines to treat swelling, sores, jaundice, inflammatory diseases, kidney disorders, diabetes and viral hepatitis, while its pharmacological and biochemical mechanisms underlying its anti-inflammatory properties have not been well investigated. The present study was carried out to investigate the effects of 80% ethanolic extract of P. amarus on pro-inflammatory mediators release in nuclear factor-kappa B (NF-кB), mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Akt (PI3K-Akt) signaling activation in lipopolysaccharide (LPS)-induced U937 human macrophages.

    METHODS: The release of prostaglandin E2 (PGE2) and pro-inflammatory cytokines, tumor necrosis factor (TNF)-α and interleukin (IL)-1β in a culture supernatant was determined by ELISA. Determination of cyclooxygenase-2 (COX-2) protein and the activation of MAPKs molecules (JNK, ERK and p38 MAPK), NF-κB and Akt in LPS-induced U937 human macrophages were investigated by immunoblot technique. The relative gene expression levels of COX-2 and pro-inflammatory cytokines were measured by using qRT-PCR. The major metabolites of P. amarus were qualitatively and quantitatively analyzed in the extract by using validated reversed-phase high performance liquid chromatography (HPLC) methods.

    RESULTS: P. amarus extract significantly inhibited the production of pro-inflammatory mediators (TNF-α, IL-1β, PGE2) and COX-2 protein expression in LPS-induced U937 human macrophages. P. amarus-pretreatment also significantly downregulated the increased mRNA transcription of pro-inflammatory markers (TNF-α, IL-1β, and COX-2) in respective LPS-induced U937 macrophages. It downregulated the phosphorylation of NF-κB (p65), IκBα, and IKKα/β and restored the degradation of IκBα, and attenuated the expression of Akt, JNK, ERK, and p38 MAPKs phosphorylation in a dose-dependent manner. P. amarus extract also downregulated the expression of upstream signaling molecules, TLR4 and MyD88, which play major role in activation of NF-κB, MAPK and PI3K-Akt signaling pathways. The quantitative amounts of lignans, phyllanthin, hypophyllahtin and niranthin, and polyphenols, gallic acid, geraniin, corilagin, and ellagic acid in the extract were determined by HPLC analysis.

    CONCLUSION: The study revealed that P. amarus targeted the NF-κB, MAPK and PI3K-Akt signaling pathways to exert its anti- inflammatory effects by downregulating the prospective inflammatory signaling mediators.

  19. Harikrishnan H, Jantan I, Haque MA, Kumolosasi E
    Phytother Res, 2018 Dec;32(12):2510-2519.
    PMID: 30238535 DOI: 10.1002/ptr.6190
    Phyllanthin, a lignan from Phyllanthus species, has been reported to possess potent immunosuppressive properties on immune cells and on adaptive and innate immune responses in animal models. Herein, we investigated the inhibitory effects of phyllanthin isolated from Phyllanthus amarus on nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and PI3K-Akt signal transducing pathways in LPS-activated U937 cells. The lipopolysaccharide-stimulated excess production of prostaglandin was significantly suppressed by phyllanthin via the mechanisms linked to the modulatory effects of cyclooxygenase 2 protein and gene expression. Phyllanthin also significantly inhibited the release and mRNA expression of proinflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha). Phyllanthin also significantly downregulated the phosphorylation of IκBα, NF-κB (p65), and IKKα/β and suppressed the activation of JNK, ERK, p38MAPK, and Akt in a concentration-dependent manner. Additionally, phyllanthin downregulated the expression of upstream signaling molecules including MyD88 and toll-like receptor 4 that are essential for the activation of NF-κB, MAPKs, and PI3K-Akt signal transducing pathways. Based on these observations, phyllanthin may exert their suppressive effects on inflammatory process by mediating the release of inflammatory signaling molecules via the NF-κB, MAPKs, and PI3K-Akt signal transducing pathways. Thus, phyllanthin holds a great promise as a potential anti-inflammatory agent to treat various inflammatory diseases.
  20. Harikrishnan H, Jantan I, Alagan A, Haque MA
    Inflammopharmacology, 2020 Feb;28(1):1-18.
    PMID: 31792765 DOI: 10.1007/s10787-019-00671-9
    The causal and functional connection between inflammation and cancer has become a subject of much research interest. Modulation of cell signaling pathways, such as those involving mitogen activated protein kinases (MAPKs), nuclear factor kappa β (NF-κB), phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt), and Wnt, and their outcomes play a fundamental role in inflammation and cancer. Activation of these cell signaling pathways can lead to various aspects of cancer-related inflammation. Hence, compounds able to modulate inflammation-related molecular targets are sought after in anticancer drug development programs. In recent years, plant extracts and their metabolites have been documented with potential in the prevention and treatment of cancer and inflammatory ailments. Plants possessing anticancer and anti-inflammatory properties due to their bioactive constituents have been reported to modulate the molecular and cellular pathways which are related to inflammation and cancer. In this review we focus on the flavonoids (astragalin, kaempferol, quercetin, rutin), lignans (phyllanthin, hypophyllanthin, and niranthin), tannins (corilagin, geraniin, ellagic acid, gallic acid), and triterpenes (lupeol, oleanolic acid, ursolic acid) of Phyllanthus amarus, which exert various anticancer and anti-inflammatory activities via perturbation of the NF-κB, MAPKs, PI3K/Akt, and Wnt signaling networks. Understanding the underlying mechanisms involved may help future research to develop drug candidates for prevention and new treatment for cancer and inflammatory diseases.
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