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  1. Zakaria ZA, Hussain MK, Mohamad AS, Abdullah FC, Sulaiman MR
    Biol Res Nurs, 2012 Jan;14(1):90-7.
    PMID: 21278166 DOI: 10.1177/1099800410395378
    Ficus deltoidea (Family Moraceae) leaves have been used traditionally by the Malays to treat ailments such as wounds, sores, and rheumatism. The aim of the present study was to determine the anti-inflammatory activity of the aqueous extract of F. deltoidea leaf (FDA) using acute and chronic inflammatory models. FDA, in the doses of 30, 100, and 300 mg/kg, was administered intraperitoneally in rats (n = 6) before the animals were subjected to the carrageenan-induced paw edema test, cotton pellet-induced granuloma test, and formalin test. The first two tests represent acute and chronic models of inflammation, respectively. The first and second phases of the formalin test represent neurogenic pain and inflammatory-mediated pain, respectively; thus, only the second phase was measured in the present study. Results showed that FDA exerted significant (p < .05) anti-inflammatory activity in all assays, with dose-response effects seen in the paw edema and formalin tests. In conclusion, the leaf of F. deltoidea possesses anti-inflammatory activity against acute and chronic inflammatory responses and against pain-associated inflammatory response. These findings justify the traditional uses of F. deltoidea leaves for treatment of inflammatory-mediated ailments.
  2. Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, et al.
    Fitoterapia, 2008 Dec;79(7-8):557-61.
    PMID: 18672036 DOI: 10.1016/j.fitote.2008.06.005
    The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.
  3. Naomi R, Bahari H, Yazid MD, Othman F, Zakaria ZA, Hussain MK
    Int J Mol Sci, 2021 Oct 06;22(19).
    PMID: 34639164 DOI: 10.3390/ijms221910816
    Hyperglycemia is a condition with high glucose levels that may result in dyslipidemia. In severe cases, this alteration may lead to diabetic retinopathy. Numerous drugs have been approved by officials to treat these conditions, but usage of any synthetic drugs in the long term will result in unavoidable side effects such as kidney failure. Therefore, more emphasis is being placed on natural ingredients due to their bioavailability and absence of side effects. In regards to this claim, promising results have been witnessed in the usage of Ipomoea batatas (I. batatas) in treating the hyperglycemic and dyslipidemic condition. Thus, the aim of this paper is to conduct an overview of the reported effects of I. batatas focusing on in vitro and in vivo trials in reducing high glucose levels and regulating the dyslipidemic condition. A comprehensive literature search was performed using Scopus, Web of Science, Springer Nature, and PubMed databases to identify the potential articles on particular topics. The search query was accomplished based on the Boolean operators involving keywords such as (1) Beneficial effect OR healing OR intervention AND (2) sweet potato OR Ipomoea batatas OR traditional herb AND (3) blood glucose OR LDL OR lipid OR cholesterol OR dyslipidemia. Only articles published from 2011 onwards were selected for further analysis. This review includes the (1) method of intervention and the outcome (2) signaling mechanism involved (3) underlying mechanism of action, and the possible side effects observed based on the phytoconstiuents isolated. The comprehensive literature search retrieved a total of 2491 articles using the appropriate keywords. However, on the basis of the inclusion and exclusion criteria, only 23 articles were chosen for further review. The results from these articles indicate that I. batatas has proven to be effective in treating the hyperglycemic condition and is able to regulate dyslipidemia. Therefore, this systematic review summarizes the signaling mechanism, mechanism of action, and phytoconstituents responsible for those activities of I. batatas in treating hyperglycemic based on the in vitro and in vivo study.
  4. Kamisan FH, Yahya F, Mamat SS, Kamarolzaman MF, Mohtarrudin N, Kek TL, et al.
    PMID: 24708543 DOI: 10.1186/1472-6882-14-123
    Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats.
  5. Zakaria ZA, Mohamed AM, Jamil NS, Rofiee MS, Hussain MK, Sulaiman MR, et al.
    Am J Chin Med, 2011;39(1):183-200.
    PMID: 21213408
    The in vitro antiproliferative and antioxidant activities of the aqueous, chloroform and methanol extracts of Muntingia calabura leaves were determined in the present study. Assessed using the 3,(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay, the aqueous and methanol extracts of M. calabura inhibited the proliferation of MCF-7, HeLa, HT-29, HL-60 and K-562 cancer cells while the chloroform extract only inhibited the proliferation of MCF-7, HeLa, HL-60 and K-562 cancer cells. Interestingly, all extracts of M. calabura, which failed to inhibit the MDA-MB-231 cells proliferation, did not inhibit the proliferation of 3T3 (normal) cells, indicating its safety. All extracts (20, 100 and 500 μg/ml) were found to possess antioxidant activity when tested using the DPPH radical scavenging and superoxide scavenging assays with the methanol, followed by the aqueous and chloroform, extract exhibiting the highest antioxidant activity in both assays. The total phenolic content for the aqueous, methanol and chloroform extracts were 2970.4 ± 6.6, 1279.9 ± 6.1 and 2978.1 ± 4.3 mg/100 g gallic acid, respectively. In conclusion, the M. calabura leaves possess potential antiproliferative and antioxidant activities that could be attributed to its high content of phenolic compounds, and thus, needs to be further explored.
  6. Bello RO, Chin VK, Abd Rachman Isnadi MF, Abd Majid R, Atmadini Abdullah M, Lee TY, et al.
    Int J Mol Sci, 2018 Apr 11;19(4).
    PMID: 29641433 DOI: 10.3390/ijms19041149
    The recently identified cytokines-interleukin (IL)-35 and interleukin (IL)-37-have been described for their anti-inflammatory and immune-modulating actions in numerous inflammatory diseases, auto-immune disorders, malignancies, infectious diseases and sepsis. Either cytokine has been reported to be reduced and in some cases elevated and consequently contributed towards disease pathogenesis. In view of the recent advances in utilizing cytokine profiles for the development of biological macromolecules, beneficial in the management of certain intractable immune-mediated disorders, these recently characterized cytokines (IL-35 and IL-37) offer potential as reasonable targets for the discovery of novel immune-modulating anti-inflammatory therapies. A detailed comprehension of their sophisticated regulatory mechanisms and patterns of expression may provide unique opportunities for clinical application as highly selective and target specific therapeutic agents. This review seeks to summarize the recent advancements in discerning the dynamics, mechanisms, immunoregulatory and anti-inflammatory actions of IL-35 and IL-37 as they relate to disease pathogenesis.
  7. Bello RO, Abdullah MA, Abd Majid R, Chin VK, Abd Rachman Isnadi MF, Ibraheem ZO, et al.
    Malar J, 2019 Dec 19;18(1):434.
    PMID: 31856836 DOI: 10.1186/s12936-019-3070-x
    BACKGROUND: The immune modulating potential of IL-35 in multiple human disorders has been reported. Consequent upon the recognition of inflammatory cytokine activation and its preponderance for mediating pathology during malaria infection, the study aimed to characterize the expression and functional contribution(s) of IL-35 in Plasmodium berghei (strain ANKA) infected mice.

    METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.

    RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.

    CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.

  8. Hisamuddin ASB, Naomi R, Bin Manan KA, Bahari H, Yazid MD, Othman F, et al.
    Front Pharmacol, 2023;14:1132087.
    PMID: 37077809 DOI: 10.3389/fphar.2023.1132087
    This study assessed the toxicity of lutein-rich purple sweet potato leaf (PSPL) extract in male Sprague-Dawley rats. Methods and study design: A total of 54 adult male Sprague-Dawley rats were used. For the acute toxicity study, three rats in the acute control group were fed 2,000 mg/kg of PSPL for 14 days. The subacute toxicity study included six rats each in four groups administered 50, 250, 500, or 1,000 mg/kg for 28 days and observed for further 14 days without treatment in the subacute control and subacute satellite groups. Changes in body weight; blood biochemistry; hematological parameters; relative organ weight; and histological sections of the heart, kidney, liver, pancreas, aorta, and retina were observed for signs of toxicity. Results: The gradual increase in weekly body weight, normal level full blood count, normal liver and kidney profile, relative organ weight, and histological sections of all stained organ tissue in the treated group compared with the acute, subacute, and satellite control groups demonstrated the absence of signs of toxicity. Conclusion: Lutein-rich PSPL extract shows no signs of toxicity up to 2,000 mg/kg/day.
  9. Hisamuddin ASB, Naomi R, Manan KAB, Bahari H, Othman F, Embong H, et al.
    Front Pharmacol, 2023;14:1175907.
    PMID: 37274105 DOI: 10.3389/fphar.2023.1175907
    The objective of this study is to access the effect of purple sweet potato leaf (PSPL) extract on diabetic retinopathy (DR) of streptozotocin (STZ)-induced male Sprague-Dawley (SD) rats. In this study, rats were injected intraperitoneally with a single dose of 60 mg/kg STZ, and diabetes was confirmed on day 7. Rats were further divided into a few groups, which were then orally administered with one of the following treatments: 25 mg/kg of gliclazide (D25G), 200 mg/kg of PSPL extract (DT 200), and 400 mg/kg of PSPL extract (DT 400). However, the normal control (NS) and control group for diabetic (DNS) were given normal saline (NS) for 12 weeks. The results show that the treated group demonstrated a reduction in serum oral glucose tolerance test (OGTT) levels of DT 200 and DT 400, and an increase in the serum and retinal insulin levels, and restored oxidative stress markers in serum and retina on week 12. The PSPL extract exhibited protective effects in maintaining the kidney, liver, retina, and pancreas architecture in 400 mg/kg compared to the 200 mg/kg treated group and D25G, thereby restoring fully transparent lenses in diabetes-induced rats. In conclusion, 400 mg/kg PSPL is the most effective dose for the amelioration of STZ-induced DR pathology in male SD rats.
  10. Alarabei AA, Abd Aziz NAL, Ab Razak NI, Abas R, Bahari H, Abdullah MA, et al.
    Adv Pharm Bull, 2024 Mar;14(1):105-119.
    PMID: 38585461 DOI: 10.34172/apb.2024.001
    Phytochemicals are compounds found in plants that possess a variety of bioactive properties, including antioxidant and immunomodulatory properties. Recent studies have highlighted the potential of phytochemicals in targeting specific signalling pathways involved in cytokine storm, a life-threatening clinical condition resulting from excessive immune cell activation and oversupply of proinflammatory cytokines. Several studies have documented the immunomodulatory effects of phytochemicals on immune function, including their ability to regulate essential cellular and molecular interactions of immune system cells. This makes them a promising alternative for cytokine storm management, especially when combined with existing chemotherapies. Furthermore, phytochemicals have been found to target multiple signalling pathways, including the TNF-α/NF-κB, IL-1/NF-κB, IFN-γ/JAK/STAT, and IL-6/JAK-STAT. These pathways play critical roles in the development and progression of cytokine storm, and targeting them with phytochemicals represents a promising strategy for controlling cytokine release and the subsequent inflammation. Studies have also investigated certain families of plant-related constituents and their potential immunomodulatory actions. In vivo and in vitro studies have reported the immunomodulatory effects of phytochemicals, which provide viable alternatives in the management of cytokine storm syndrome. The collective data from previous studies suggest that phytochemicals represent a potentially functional source of cytokine storm treatment and promote further exploration of these compounds as immunomodulatory agents for suppressing specific signalling cascade responses. Overall, the previous research findings support the use of phytochemicals as a complementary approach in managing cytokine storm and improving patient outcomes.
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