Displaying publications 1 - 20 of 282 in total

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  1. Wang S, Yang J, Kuang X, Li H, Du H, Wu Y, et al.
    J Ethnopharmacol, 2024 May 23;326:117913.
    PMID: 38360380 DOI: 10.1016/j.jep.2024.117913
    ETHNOPHARMACOLOGICAL RELEVANCE: Kaempferia galanga Linn. is an aromatic medicinal herb with extensively applied in India, China, Malaysia and other South Asia countries for thousands of years. It has been mentioned to treat abdominal tumors. Ethyl cinnamate (EC), one of the main chemical constituents of the rhizome of K. galanga, exhibited nematocidal, sedative and vasorelaxant activities. However, its anti-angiogenic activity, and anti-tumor effect have not been investigated.

    AIM OF THE STUDY: To investigate the anti-angiogenic mechanism of EC and its anti-tumor effect by suppressing angiogenesis.

    MATERIALS AND METHODS: The in vitro anti-angiogenic effect was evaluated using HUVECs model induced by VEGF and zebrafish model in vivo. The influence of the EC on phosphorylation of VEGFR2 and its downstream signaling pathways were evaluated by western blotting assay. Molecule docking technology was conducted to explore the interaction between EC and VEGFR2. SPR assay was used for detecting the binding affinity between EC and VEGFR2. To further investigate the molecular mechanism of EC on anti-angiogenesis, VEGFR2 knockdown in HUVECs and examined the influence of the EC. Anti-tumor activity of EC was evaluated using colony formation assay and apoptosis assay. The inhibitory effect of EC on tumor growth was explored using HT29 colon cancer xenograft model.

    RESULTS: EC obviously inhibited proliferation, migration, invasion and tube formation of VEGF-induced HUVECs. EC also induced apoptosis of HUVECs. Moreover, it inhibited the development of vessel formation in zebrafish. Further investigations demonstrated that EC could suppress the phosphorylation of VEGFR2, and its downstream signaling pathways were altered in VEGF-induced HUVECs. EC formed a hydrogen bond to bind with the ATP binding site of the VEGFR2, and EC-VEGFR2 interaction was shown in SPR assay. The suppressive effect of EC on angiogenesis was abrogated after VEGFR2 knockdown in HUVECs. EC inhibited the colon cancer cells colony formation and induced apoptosis. In addition, EC suppressed tumor growth in colon cancer xenograft model, and no detectable hepatotoxicity and nephrotoxicity. In addition, it inhibited the phosphorylation of VEGFR2, and its downstream signal pathways in tumor.

    CONCLUSIONS: EC could inhibit tumor growth in colon cancer by suppressing angiogenesis via VEGFR2 signaling pathway, and suggested EC as a promising candidate for colon cancer treatment.

  2. Fauzi A, Kifli N, Noor MHM, Hamzah H, Azlan A
    J Ethnopharmacol, 2024 May 10;325:117914.
    PMID: 38360381 DOI: 10.1016/j.jep.2024.117914
    ETHNOPHARMACOLOGICAL RELEVANCE: Traditional uses of Morus alba L. leaf extracts (MLE) have been reported for treating hyperglycaemia and diabetes. Phytochemical compounds in the leaves demonstrated the ability to enhance insulin sensitivity and β-cell secretory function, suggesting their potential value in reducing blood glucose and treating diabetes. However, the phytochemical constituents and safety of the herbal medicines need to be verified in each experimental field from different growing areas. Studies on the phytochemistry and toxicity of Morus alba leaves in Southeast Asia, especially in Brunei, have never been investigated.

    AIM OF THE STUDY: This study aimed to investigate the bioactivity and phytochemistry of Morus alba ethanolic leaf extract from Brunei Darussalam and its subacute toxic effects in the Institute of Cancer Research (ICR) female mice.

    MATERIALS AND METHODS: The phenolic yield and antioxidant of the extract were analysed. Meanwhile, liquid chromatography-mass spectrometry and high-performance liquid chromatography were utilised to determine the phenolic compound of the MLE. In the subacute toxicity study, twenty-five female mice were randomly divided into five groups: the control group, which received oral gavage of 5% dimethyl sulfoxide solvent (DMSO), and the MLE treatment group, which received the extract at a dose of 125, 250, 500 and 1000 mg/kg. Physiology, haematology, biochemistry, and histology were evaluated during the study.

    RESULTS: Morus alba leaf depicted total phenolic 10.93 mg gallic acid equivalents (GAE)/g dry weight (DW), flavonoid 256.67 mg quercetin equivalents (QE)/g DW, and antioxidant bioactivity content of 602.03 IC50 μg/mL and 13.21 mg Fe2+/g DW. Twenty compounds in the Morus alba ethanolic leaf extract were identified, with chlorogenic acid (305.60 mg/100 g DW) as the primary compound. As for subacute toxicity in this study, neither mortality nor haematological changes were observed. On the other hand, administration of 500 and 1000 mg/kg MLE resulted in mild hepatocellular injury, as indicated by a significant (p 

  3. Ng MJ, Mohamad Razif MF, Kong BH, Yap HY, Ng ST, Tan CS, et al.
    J Ethnopharmacol, 2024 Mar 19;328:118073.
    PMID: 38513780 DOI: 10.1016/j.jep.2024.118073
    ETHNOPHARMACOLOGICAL RELEVANCE: Medicinal mushrooms belonging to the Lignosus spp., colloquially known as Tiger Milk mushrooms (TMMs), are used as traditional medicine by communities across various regions of China and Southeast Asia to enhance immunity and to treat various diseases. At present, three Lignosus species have been identified in Malaysia: L. rhinocerus, L. tigris, and L. cameronensis. Similarities in their macroscopic morphologies and the nearly indistinguishable appearance of their sclerotia often lead to interchangeability between them. Hence, substantiation of their traditional applications via identification of their individual bioactive properties is imperative in ensuring that they are safe for consumption. L. tigris was first identified in 2013. Thus far, studies on L. tigris cultivar sclerotia (Ligno TG-K) have shown that it possesses significant antioxidant activities and has greater antiproliferative action against selected cancer cells in vitro compared to its sister species, L. rhinocerus TM02®. Our previous genomics study also revealed significant genetic dissimilarities between them. Further omics investigations on Ligno TG-K hold immense potential in facilitating the identification of its bioactive compounds and their associated bioactivities.

    AIM OF STUDY: The overall aim of this study was to investigate the gene expression profile of Ligno TG-K via de novo RNA-seq and pathway analysis. We also aimed to identify highly expressed genes encoding compounds that contribute to its cytotoxic and antioxidant properties, as well as perform a comparative transcriptomics analysis between Ligno TG-K and its sister species, L. rhinocerus TM02®.

    MATERIALS AND METHODS: Total RNA from fresh 3-month-old cultivated L. tigris sclerotia (Ligno TG-K) was extracted and analyzed via de novo RNA sequencing. Expressed genes were analyzed using InterPro and NCBI-Nr databases for domain identification and homology search. Functional categorization based on gene functions and pathways was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Clusters of Orthologous Genes (COG) databases. Selected genes were subsequently subjected to phylogenetic analysis.

    RESULTS: Our transcriptomics analysis of Ligno TG-K revealed that 68.06% of its genes are expressed in the sclerotium; 80.38% of these were coding transcripts. Our analysis identified highly expressed transcripts encoding proteins with prospective medicinal properties. These included serine proteases (FPKM = 7356.68), deoxyribonucleases (FPKM = 3777.98), lectins (FPKM = 3690.87), and fungal immunomodulatory proteins (FPKM = 2337.84), all of which have known associations with anticancer activities. Transcripts linked to proteins with antioxidant activities, such as superoxide dismutase (FPKM = 1161.69) and catalase (FPKM = 1905.83), were also highly expressed. Results of our sequence alignments revealed that these genes and their orthologs can be found in other mushrooms. They exhibit significant sequence similarities, suggesting possible parallels in their anticancer and antioxidant bioactivities.

    CONCLUSION: This study is the first to provide a reference transcriptome profile of genes expressed in the sclerotia of L. tigris. The current study also presents distinct COG profiles of highly expressed genes in Ligno TG-K and L. rhinocerus TM02®, highlighting that any distinctions uncovered may be attributed to their interspecies variations and inherent characteristics that are unique to each species. Our findings suggest that Ligno TG-K contains bioactive compounds with prospective medicinal properties that warrant further investigations.

    CLASSIFICATION: Systems biology and omics.

  4. Hikmawanti NPE, Saputri FC, Yanuar A, Jantan I, Ningrum RA, Mun'im A
    J Ethnopharmacol, 2024 Feb 10;320:117387.
    PMID: 37944874 DOI: 10.1016/j.jep.2023.117387
    ETHNOPHARMACOLOGICAL RELEVANCE: Pluchea indica (L.) Less (family Asteraceae) is popularly consumed as a medicinal vegetable and used in ethnomedicine to treat various diseases including gastrointestinal problems such as dysentery and leucorrhoea, which are due to bacterial, fungal or parasitic infections. There have been numerous studies on the antimicrobial effects of the plant due to these ethnomedicine use.

    AIM OF THIS REVIEW: This review is comprehensively discussed the information on the anti-infective properties of P. indica and its secondary metabolites, and highlight the potential of the plant as a new source of anti-infective agents.

    MATERIALS AND METHODS: Scientific databases such as Scopus, Google Scholar, ScienceDirect, PubMed, Wiley Online Library, and ACS Publications were used to gather the relevant information on the ability of P. indica to fight infections, with the leaves and roots receiving most of the attention.

    RESULTS: Anti-bacterial, anti-mycobacterial, anti-malarial, and anti-viral activities have been the most exploited. Most studies were carried out on the crude extracts of the plant and in most studies the bioactive extracts were not standardized or chemically characterized. Several studies have reported the anti-infective activity of several bioactive components of P. indica including caffeoylquinic acids, terpenoid glycosides, thiophenes, and kaempferol.

    CONCLUSIONS: The strong anti-infective effect and underlying mechanisms of the compounds provide insights into the potential of P. indica as a source of new leads for the development of anti-infective agents for use in food and pharmaceutical industries.

  5. Dewi IP, Dachriyanus, Aldi Y, Ismail NH, Hefni D, Susanti M, et al.
    J Ethnopharmacol, 2024 Feb 10;320:117381.
    PMID: 37967776 DOI: 10.1016/j.jep.2023.117381
    ETHNOPHARMACOLOGICAL RELEVANCE: Garcinia cowa Roxb. is called asam kandis in West Sumatra. This plant contains several quinone compounds, including tetraprenyltoluquinone (TPTQ). The bioactivity of this compound has been tested as an anticancer agent. However, reports regarding its anti-inflammatory effects are still limited, especially against coronavirus disease (Covid-19).

    AIM OF THE STUDY: This study explores the anti-inflammatory effect of TPTQ in silico, in vitro, and in vivo.

    MATERIALS AND METHODS: In silico testing used the Gnina application, opened via Google Colab. The TPTQ structure was docked with the nuclear factor kappa B (NF-ĸB) protein (PDB: 2RAM). In vitro testing began with testing the cytotoxicity of TPTQ against Raw 264.7 cells, using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A phagocytic activity test was carried out using the neutral red uptake method, and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion tests were carried out using the enzyme-linked immunosorbent assay (ELISA) method. In vivo, tests were carried out on mice by determining cluster of differentiation 8+ (CD8+), natural killer cell (NK cell), and IL-6 parameters, using the ELISA method.

    RESULTS: TPTQ has a lower binding energy than the native ligand and occupies the same active site as the native ligand. TPTQ decreased the phagocytosis index and secretion of IL-6 and TNF-α experimentally in vitro. TPTQ showed significant downregulation of CD8+ and slightly decreased NK cells and IL-6 secretion in vivo.

    CONCLUSION: The potent inhibitory effect of TPTQ on the immune response suggests that TPTQ can be developed as an anti-inflammatory agent, especially in the treatment of Covid-19.

  6. Jabbari S, Zakaria ZA, Ahmadimoghaddam D, Mohammadi S
    J Ethnopharmacol, 2024 Jan 30;319(Pt 1):117181.
    PMID: 37734474 DOI: 10.1016/j.jep.2023.117181
    ETHNOPHARMACOLOGICAL RELEVANCE: Lotus corniculatus L. (Fabaceae) traditionally used in Persian folk medicine to heal peritoneal inflammation and back pain.

    AIM OF THE STUDY: To explore the antinociceptive (acute pain) and anti-neuropathic (chronic pain) activities of Lotus corniculatus leaves essential oil (LCEO) in addition to uncovering the possible mechanisms of antinociception.

    MATERIALS AND METHODS: LCEO as well as the pure oleanolic acid (OA) compound, were assayed for their effects on acute (formalin induced paw licking test or FIPT) and chronic (cervical contusion injury models on the fifth cervical vertebra or CCS; 14-day intervals) pain. The possible involvements of NO-cGMP-K+ channel, TRPV, dopamine, cannabinoid, PPAR, adrenergic, and opioid mechanisms in the antinociceptive activity of LCEO have studied by formalin test. The levels of p53 and inflammatory markers were measured using a streptavidin biotin immune peroxidase complex and ELISA methods, respectively.

    RESULTS: The LCEO and OA exerted antinociceptive activity in the first-phase of FIPT. Pretreatment with antagonists of TRPV1, dopamine D2, cannabinoid type1 and 2, and NO-cGMP-K+ channel blockers (glibenclamide, L-NAME and methylene blue) attenuated the antinociceptive effect of LCEO in FIPT. In addition, LCEO and OA meaningfully reduced hyperalgesia (days 6-14) and mechanical allodynia (days 2-14) in the CCS model. LCEO suppressed the apoptotic marker (p53) in CCS model and also ameliorated IL-2, TNF-α, and IL-1 in the spinal cord.

    CONCLUSION: Finally, LCEO inhibited acute (possibly via the modulation of opioid, TRPV, dopamine, cannabinoid mechanisms as well as NO-cGMP-K+ channel) and chronic pain (via suppressing apoptotic and inflammatory markers) in male rats. The results also suggest that OA has analgesic activity against acute and chronic pain conditions.

  7. Sulaiman I, Okwuofu EO, Mohtarrudin N, Lim JCW, Stanslas J
    J Ethnopharmacol, 2024 Jan 30;319(Pt 1):117082.
    PMID: 37652197 DOI: 10.1016/j.jep.2023.117082
    ETHNOPHARMACOLOGICAL RELEVANCE: Andrographis paniculata Burm. Nees (AP) is an herb used traditionally in Indian and Chinese traditional medicine for the treatment of various inflammatory and respiratory tract diseases. However, the anti-inflammatory potential of standardized Andrographis paniculata 50% ethanol extract (APEE50) in the murine model of asthma has not been investigated.

    AIM OF THE STUDY: This study aimed to evaluate the protective anti-inflammatory potential and better understand the underlying mechanism of action of APEE50 in a clinically-relevant mouse asthma model. Thereafter, develop the ethanolic extract of AP as a supplement for asthma prophylaxis.

    MATERIALS AND METHOD: APEE50 was prepared and standardized for AGP, NAG, and DDAG using a high-performance liquid chromatography system. Asthma was induced according to a 14-day house dust mite (HDM) induction protocol. The prophylactic potential of APEE50 (50 mg/kg - 200 mg/kg) was determined by assessing cardinal asthma features, which included BALF leukocyte and differential cell count, BALF cytokine assay, histology, gene expression, and airway hyperreactivity study.

    RESULTS: APEE50 significantly inhibited HDM-induced airway eosinophilia and neutrophilia. In addition to decreased levels of IL-4, IL-5, IL-13, and eotaxin in bronchoalveolar fluid, APEE50 abrogated HDM-induced airway mucus over-secretion and airway hyper-responsiveness. Administration of APEE50 downregulated HDM-induced upregulation of the oxidative stress enzyme Duox1 (dual oxidase 1) and marginally induced Nfe2l2 (nuclear factor erythroid 2-related factor 2) gene expressions. Similarly, Th2-related (Serpinb2, Clca3a1, Il4 and Il13) and Muc5ac gene expression were significantly downregulated.

    CONCLUSION: Prophylactic administration of APEE50 prevented the progression of HDM-induced asthmatic responses by down-regulating Th2 cytokine gene expression and oxidative stress level.

  8. Zuhri UM, Yuliana ND, Fadilah F, Erlina L, Purwaningsih EH, Khatib A
    J Ethnopharmacol, 2024 Jan 30;319(Pt 3):117296.
    PMID: 37820996 DOI: 10.1016/j.jep.2023.117296
    ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure.

    AIM OF THE STUDY: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation.

    MATERIALS AND METHODS: We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools.

    RESULTS: The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds.

    CONCLUSIONS: Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.

  9. Wong PL, Zolkeflee NKZ, Ramli NS, Tan CP, Azlan A, Tham CL, et al.
    J Ethnopharmacol, 2024 Jan 10;318(Pt B):117015.
    PMID: 37572932 DOI: 10.1016/j.jep.2023.117015
    ETHNOPHARMACOLOGICAL RELEVANCE: Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models.

    AIM OF THE STUDY: To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (1H-NMR)-based metabolomics approach.

    MATERIALS AND METHODS: Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted 1H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.

    RESULTS: Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.

    CONCLUSIONS: This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.

  10. Mararajah S, Giribabu N, Salleh N
    J Ethnopharmacol, 2024 Jan 10;318(Pt B):117026.
    PMID: 37572930 DOI: 10.1016/j.jep.2023.117026
    ETHNOPHARMACOLOGICAL RELEVANCE: Chlorophytum borivilianum (C. borivilianum) (CB) has traditionally been used to treat male sexual dysfunctions and has been claimed to possess aphrodisiac properties.

    AIM OF THE STUDY: To investigate the ability of CB to ameliorate H2O2-induced oxidative stress in testes and sperm in mice and prevent H2O2-induced oxidative in human sperm.

    MATERIALS AND METHODS: Oxidative stress was induced in male mice by pre-exposure to 2% H2O2 orally for seven consecutive days, followed by 100 and 200 mg/kg b. w. administration. CB for another seven days. At the end of treatment, mice were sacrificed and testes and epididymal sperm were harvested. Serum FSH, LH and testosterone levels were measured and sperm parameters were obtained. Meanwhile, oxidative stress levels in mice testes and sperm, steroidogenesis and spermatogenesis markers in mice testes were assessed by molecular biological techniques. In another experiment, sperm from thirty-two healthy fertile men were incubated with 200 μM H2O2 and CB (100 and 200 μg/ml) simultaneously and were then evaluated for sperm parameter changes.

    RESULTS: In mice, CB administration ameliorates persistent increases in oxidative stress and decreases in anti-oxidative enzyme levels in testes and sperm following H2O2 pre-exposure. Additionally, CB also helps to ameliorate deterioration in sperm parameters and testicular steroidogenesis and spermatogenesis and restores the serum FSH, LH and testosterone levels near normal in mice. In humans, CB helps to prevent deterioration in sperm parameters following H2O2 exposure.

    CONCLUSION: CB is potentially useful to preserve the male reproductive capability and subsequently male fertility in high oxidative stress conditions.

  11. Sabry MM, Abdel-Rahman RF, Fayed HM, Taher AT, Ogaly HA, Albohy A, et al.
    J Ethnopharmacol, 2023 Oct 05;314:116631.
    PMID: 37172920 DOI: 10.1016/j.jep.2023.116631
    ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus maculata Hook from the Myrtaceae family is a native Australian plant that is frequently cultivated in Egypt. Many Eucalyptus species, including E. maculata, were widely used by the Dharawal, the indigenous Australian people, for their anti-inflammatory properties.

    AIM OF THE STUDY: The purpose of this study was to determine the anti-inflammatory activity of the ethanol extract of E. maculata resin exudate, its methylene chloride and n-butanol fractions, as well as the isolated compounds.

    MATERIALS AND METHODS: the ethanol extract was partitioned by methylene chloride, and n-butanol saturated with water. The fractions were chromatographed to isolate pure compounds. In-vivo anti-inflammatory activity of the ethanol extract, the fractions at a dose of 200 mg/kg, and the isolated compounds (20 mg/kg) was estimated using carrageenan-induced rat paws edema method against indomethacin (20 mg/kg). The activity was supported by histopathological and biochemical parameters.

    RESULTS: Three isolated compounds were identified as aromadendrin (C1), 7-O-methyl aromadendrin (C2), and naringenin (C3). Our findings demonstrated that the tested fractions significantly reduced the paw edema starting from the 3rd to the 5th hour as compared to the positive control, compounds C2 and C3 showed the greatest significant reduction in paw edema. The ethanol extract, fractions, C2, and C3 demonstrated an anti-inflammatory potential through reducing the levels of TNF-α, IL-6, and PGE2, as well as COX-2 protein expression compared to the negative control. These results were supported by molecular docking, which revealed that the isolated compounds had high affinity to target COX-1 and COX-2 active sites with docking scores ranging from -7.3 to -9.6 kcal mol-1 when compared to ibubrofen (-7.8 and -7.4 kcal mol-1, respectively). Molecular dynamics simulations were also performed and confirmed the docking results.

    CONCLUSION: The results supported the traditional anti-inflammatory potency of E. maculata Hook, and the biochemical mechanisms underlying this activity were highlighted, opening up new paths for the development of potent herbal anti-inflammatory medicine. Finally, our findings revealed that E. maculata resin constituents could be considered as promising anti-inflammatory drug candidates.

  12. Kumar GG, Kilari EK, Nelli G, Bin Salleh N
    J Ethnopharmacol, 2023 Oct 05;314:116638.
    PMID: 37187362 DOI: 10.1016/j.jep.2023.116638
    ETHNOPHARMACOLOGICAL RELEVANCE: Turnera diffusa Willd. ex Schult. (T. diffusa) has traditionally been used to treat male reproductive dysfunction and have aphrodisiac properties.

    AIMS OF THE STUDY: This study aims to investigate the ability of T. diffusa to ameliorate the impairment in testicular steroidogenesis and spermatogenesis in DM that might help to improve testicular function, and subsequently restore male fertility.

    MATERIALS AND METHODS: DM-induced adult male rats were given 100 mg/kg/day and 200 mg/kg/day T. diffusa leaf extract orally for 28 consecutive days. Rats were then sacrificed; sperm and testes were harvested and sperm parameter analysis were performed. Histo-morphological changes in the testes were observed. Biochemical assays were performed to measure testosterone and testicular oxidative stress levels. Immunohistochemistry and double immunofluorescence were used to monitor oxidative stress and inflammation levels in testes as well as Sertoli and steroidogenic marker proteins' expression.

    RESULTS: Treatment with T. diffusa restores sperm count, motility, and viability near normal and reduces sperm morphological abnormalities and sperm DNA fragmentation in diabetic rats. T. diffusa treatment also reduces testicular NOX-2 and lipid peroxidation levels, increases testicular antioxidant enzymes (SOD, CAT, and GPx) activities, ameliorates testicular inflammation via downregulating NF-ΚB, p-Ikkβ and TNF-α and upregulating IκBα expression. In diabetic rats, T. diffusa treatment increases testicular steroidogenic proteins (StAR, CYP11A1, SHBG, and ARA54, 3 and 17β-HSD) and plasma testosterone levels. Furthermore, in diabetic rats treated with T. diffusa, Sertoli cell marker proteins including Connexin 43, N-cadherin, and occludin levels in the testes were elevated.

    CONCLUSION: T. diffusa treatment could help to ameliorate the detrimental effects of DM on the testes, thus this plant has potential to be used to restore male fertility.

  13. Zhang X, Zhao L, Xiang S, Sun Y, Wang P, Chen JJ, et al.
    J Ethnopharmacol, 2023 May 10;307:116243.
    PMID: 36791927 DOI: 10.1016/j.jep.2023.116243
    ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Tongluo formula (YSTLF) is formulated based on traditional Chinese medicine theory for the treatment of Diabetic kidney disease (DKD) and has been shown to be effective in improving the symptoms of DKD according to the clinical observation.

    AIM OF THE STUDY: To explore the effect of YSTLF on DKD and figure out whether its effects were due to the regulation Sirt6/TGF-β1/Smad2/3 pathway and promoting degradation of TGF-β1.

    MATERIALS AND METHODS: The extract of YSTLF at 1, 2.5 and 5 g/kg was orally administered to C57BLKS/J (db/db) mice for 8 weeks and db/db mice were given valsartan as a positive control. The littermate db/m and db/db mice were given vehicle as the control and model group, respectively. Blood urea nitrogen and serum creatinine were detected and the urinary albumin excretion, urea albumin creatinine ratio was calculated. The histopathological change of renal tissues in each group was determined. Simultaneously, the levels of fibrosis-related proteins and messenger RNA (mRNA) in kidney and high glucose (HG)-induced SV40-MES-13 cells were detected. The roles of YSTLF in regulating of Sirt6/TGF-β1/Smad2/3 signaling pathway were investigated in HG-stimulated SV40-MES-13 cells and validated in db/db mice. Furthermore, the effect of YSTLF on TGF-β1 degradation was investigated in HG-stimulated SV40-MES-13 cells.

    RESULTS: YSTLF significantly improved the renal function in DKD mice. YSTLF dose-dependently attenuated pathological changes and suppressed the expression of type I collagen, alpha smooth muscle actin, type IV collagen, and fibronectin in vitro and in vivo, resulting in ameliorating of renal fibrosis. YSTLF positively regulated Sirt6 expression, while inhibited the activating of TGF-β1/Smad2/3 signaling pathway. TGF-β1 was steady expressed in HG-stimulated SV40-MES-13 cells, whereas was continuously degraded under YSTLF treatment.

    CONCLUSIONS: YSTLF significantly ameliorates renal damages and fibrosis may via regulating Sirt6/TGF-β1/Smad2/3 signaling pathway as well as promoting the degradation of TGF-β1.

  14. Ng MJ, Kong BH, Teoh KH, Yap YH, Ng ST, Tan CS, et al.
    J Ethnopharmacol, 2023 Mar 25;304:115957.
    PMID: 36509254 DOI: 10.1016/j.jep.2022.115957
    ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerus (Cooke) Ryvarden (also known as Tiger Milk mushroom, TMM), is a basidiomycete belonging to the Polyporaceae family. It has been documented to be used by traditional Chinese physicians and indigenous people in Southeast Asia to treat a variety of illnesses, such as gastritis, arthritis, and respiratory conditions, as well as to restore patients' physical well-being. TMM has also been used in folk medicine to treat cancer. For example, people from the indigenous Kensiu tribe of northeast Kedah (Malaysia) apply shredded TMM sclerotium mixed with water directly onto breast skin to treat breast cancer, while Chinese practitioners from Hong Kong, China prescribe TMM sclerotium as a treatment for liver cancer. L. rhinocerus has previously been demonstrated to possess selective anti-proliferative properties in vitro, however pre-clinical in vivo research has not yet been conducted.

    AIM OF STUDY: This study aimed to examine the anti-tumor activities of L. rhinocerus TM02®, using two different sample preparations [cold water extract (CWE) and fraction] via various routes of administration (oral and intraperitoneal) on an MCF7-xenograft nude mouse model. This study also investigated the inhibitory effect of TM02® CWE and its fractions against COX-2 in vitro using LPS-induced RAW264.7 macrophages, on the basis of the relationship between COX-2 and metastasis, apoptosis resistance, as well as the proliferation of cancer cells.

    MATERIALS AND METHODS: The first preparation, L. rhinocerus TM02® sclerotium powder (TSP) was dissolved in cold water to obtain the cold water extract (CWE). It was further fractionated based on its molecular weight to obtain the high (HMW), medium (MMW) and low (LMW) molecular weight fractions. The second preparation, known as the TM02® rhinoprolycan fraction (TRF), was obtained by combining the HMW and MMW fractions. TSP was given orally to mimic the daily consumption of a supplement; TRF was administered intraperitoneally to mimic typical tumorous cancer treatment with a rapid and more thorough absorption through the peritoneal cavity. Another experiment was conducted to examine changes in COX-2 activity in LPS-induced RAW264.7 macrophages after a 1-h pre-treatment with CWE, HMW, and MMW.

    RESULTS: Our results revealed that intraperitoneal TRF-injection (90 μg/g BW) for 20 days reduced initial tumor volume by ∼64.3% (n = 5). The percentage of apoptotic cells was marginally higher in TRF-treated mice vs. control, suggesting that induction of apoptosis as one of the factors that led to tumor shrinkage. TSP (500 μg/g BW) oral treatment (n = 5) for 63 days (inclusive of pre-treatment prior to tumor inoculation) effectively inhibited tumor growth. Four of the five tumors totally regressed, demonstrating the effectiveness of TSP ingestion in suppressing tumor growth. Although no significant changes were found in mouse serum cytokines (TNF-α, IL-5, IL-6 and CCL2), some increasing and decreasing trends were observed. This may suggest the immunomodulatory potential of these treatments that can directly or indirectly affect tumor growth. Pre-treatment with CWE, HMW and MMW significantly reduced COX-2 activity in RAW264.7 macrophages upon 24 h LPS-stimulation, suggesting the potential of L. rhinocerus TM02® extract and fractions in regulating M1/M2 polarization.

    CONCLUSION: Based on the findings of our investigation, both the rhinoprolycan fraction and crude sclerotial powder from L. rhinocerus TM02® demonstrated tumor suppressive effects, indicating that they contain substances with strong anticancer potential. The antitumor effects of L. rhinocerus TM02® in our study highlights the potential for further explorations into its mechanism of action and future development as a prophylactic or adjunct therapeutic against tumorous cancer.

  15. Kow ASF, Khoo LW, Tan JW, Abas F, Lee MT, Israf DA, et al.
    J Ethnopharmacol, 2023 Mar 01;303:116003.
    PMID: 36464074 DOI: 10.1016/j.jep.2022.116003
    ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of β-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach.

    AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE.

    MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot.

    RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model.

    CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

  16. Adam FA, Mohd N, Rani H, Mohd Yusof MYP, Baharin B
    J Ethnopharmacol, 2023 Feb 10;302(Pt A):115863.
    PMID: 36283639 DOI: 10.1016/j.jep.2022.115863
    ETHNOPHARMACOLOGICAL RELEVANCE: Salvadora persica L., also known as miswak, is an indigenous plant most prevalent in the Middle Eastern, some Asian, and African countries. It has medicinal and prophylactics function for numerous illnesses, including periodontal disease. Various trials, apart from World Health Organization encouragement have contributed to the production and use of S. persica in extract form in the formulation of mouthwash. This systematic review and meta-analysis aimed to compare the clinical effect of Salvadora persica-extract mouthwash and chlorhexidine gluconate mouthwash for anti-plaque and anti-gingivitis functions.

    METHODS: Using the PRISMA 2020 Protocol, a systematic search of the publications was undertaken from the MEDLINE, CENTRAL, Science Direct, PubMed, and Google Scholars for randomized control trials published through 31st January 2022 to determine the effectiveness of Salvadora persica-extract mouthwash relative to chlorhexidine gluconate as anti-plaque and anti-gingivitis properties.

    RESULTS: A total of 1809 titles and abstracts were screened. Of these, twenty-two studies met the inclusion criteria for the systematic review while only sixteen were selected for meta-analysis. The overall effects of standardized mean difference and 95% CI were 0.89 [95% CI 0.09 to 1.69] with a χ2 statistic of 2.54, 15 degrees of freedom (p 

  17. Sundara Rajoo K, Lepun P, Alan R, Singh Karam D, Abdu A, Rosli Z, et al.
    J Ethnopharmacol, 2023 Jan 30;301:115780.
    PMID: 36202163 DOI: 10.1016/j.jep.2022.115780
    ETHNOPHARMACOLOGICAL RELEVANCE: Sarawak is located in one of the world's most biodiverse regions and is home to more than 40 sub-ethnic groups that each have their own distinct culture, language and lifestyle. This has given rise to numerous, unique ethnobotanical systems. However, due to rapid urbanization, this traditional knowledge is at a risk of extinction. Yet, ethnobotanical studies in Sarawak are almost non-existent, especially among Orang Ulu communities like the Kenyah.

    AIM OF STUDY: Therefore, this study was conducted to document the ethnomedicinal knowledge of the Kenyah community. The main objectives of this study are: 1) To determine and document the diversity of medicinal plants used by the Kenyah community, 2) To determine whether the availability of modern medicine has affected Kenyah traditional medicine, and 3) To identify plants which have not been previously cited or used for previously unreported medical uses.

    MATERIALS AND METHODS: We conducted repeated interviews and field surveys at the Asap-Koyan Resettlement Area, Belaga Sarawak. A total of 24 respondents from four Kenyah longhouses were interviewed in this study. Individuals possessing extensive traditional medicinal knowledge were identified via preliminary interviews or by viva voce. Translators were employed to ensure that there was no miscommunication. The results were evaluated based on the plant's total use-reports and number of respondents citing the plant. The data was also evaluated based on use-reports by ailment category.

    RESULTS: Over 95% of the respondents were 40 years and older (58.21 years old ± 11.21). This was due to the younger members of the community (40 years old and below) admitting that they had almost no knowledge regarding traditional medicine, as they preferred relying on modern medicine. A total of 61 plant species were mentioned by the 24 respondents Seven plants had five or more respondents citing it, which was more than 20% of the respondents. These plants were Piper betle, Homalomena cordata, Senna alata, Annona muricata, Derris elliptica, Blumea balsamifera and Coscinium fenestratum.

    CONCLUSION: Almost all of the cited plants had been previously recorded to be used in either Ayurvedic, Chinese herbal medicine, Malay traditional medicine or other Asian ethnomedicinal systems. However, there were four highly cited species that were used for treatments that were scarcely reported in past literature. These were piper betle (used by Kenyah to treat fever), Sauropus andrognus (used by Kenyah to treat fever), Derris elliptica (used by Kenyah to treat fever and influenza) and Coscinuim fenestratum (used by Kenyah to treat toxic effects from non-medical substances).

  18. Ramli H, Nor Aripin KN, Mohd Said S, Mohamad Hanafiah R, Mohd Dom TN
    J Ethnopharmacol, 2022 Nov 15;298:115598.
    PMID: 35944735 DOI: 10.1016/j.jep.2022.115598
    ETHNOPHARMACOLOGICAL RELEVANCE: Salvadora persica L. and Azadirachtaindica A.Juss. are listed within the most common sources of miswak or chewing stick that widely used among Western Asia and Muslim populations worldwide. Miswak use in conjunction with toothbrush (adjunctive) has become apparent among the adults. Furthermore, miswak has been reported to have mechanical and pharmacological activities, and benefits to the oral health, by many studies.

    AIM OF THE STUDY: To assess the effectiveness of miswak in maintaining periodontal health among adults.

    MATERIALS AND METHODS: We searched for randomised controlled trials (RCTs) investigating the effect of miswak published in PubMed, EBSCOHOST (Dentistry & Oral Sciences), SCOPUS, and Cochrane Database for Systematic Review (CDSR) from inception to May 08, 2022. The primary outcomes of interest were changes in the periodontal health measured with plaque and gingivitis scores as well as subgingival bacteria load. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach while the estimates of effect were pooled using a random-effects model.

    RESULTS: Ten eligible articles were identified, of which 9 could be analysed quantitatively. The remaining report was included as part of the qualitative analysis. The meta-analysis showed that miswak was comparable with the toothbrush in reducing the mean plaque score (p= 0.08, SMD: 0.39, and 95% CI: -0.05 to 0.83) and mean gingivitis score (p= 0.37, SMD: 0.13, and 95% CI: -0.16 to 0.43). Even higher certainty of evidence for the effect of miswak on mean plaque reduction on labial surface of anterior teeth. However, the adjunctive effect of miswak was significantly more superior for reducing plaque (p= 0.01, SMD: 0.68, and 95% CI: 0.14 to 1.22) and gingivitis score (p= 0.04, SMD: 0.66, and 95% CI: 0.03 to 1.29).

    CONCLUSIONS: Miswak effectively reduced plaque and gingivitis scores to a level comparable to toothbrush when used exclusively. Adjunctive miswak use was particularly effective in improving periodontal health. However, the included studies inadequately reported on the method of toothbrushing using miswak and the frequency of miswak use. Therefore, further clinical studies are recommended to explore on the advantages and proper method of miswak practice for optima outcome and safety.

  19. Elgorashi EE, Eldeen IMS, Makhafola TJ, Eloff JN, Verschaeve L
    J Ethnopharmacol, 2022 Mar 01;285:114868.
    PMID: 34826541 DOI: 10.1016/j.jep.2021.114868
    ETHNOBOTANICAL RELEVANCE: Smoke from the wood of Acacia seyal Delile has been used by Sudanese women for making a smoke bath locally called Dukhan. The ritual is performed to relieve rheumatic pain, smooth skin, heal wounds and achieve general body relaxation.

    AIM OF THE STUDY: The present study was designed to investigate the in vitro anti-inflammatory effect of the smoke condensate using cyclooxygenase -1 (COX-1) and -2 (COX-2) as well as its potential genotoxic effects using the bacterial-based Ames test and the mammalian cells-based micronucleus/cytome and comet assays.

    MATERIAL AND METHODS: The smoke was prepared in a similar way to that commonly used traditionally by Sudanese women then condensed using a funnel. Cyclooxygenase assay was used to evaluate its in vitro anti-inflammatory activity. The neutral red uptake assay was conducted to determine the range of concentrations in the mammalian cells-based assays. The Ames, cytome and comet assays were used to assess its potential adverse (long-term) effects.

    RESULTS: The smoke condensate did not inhibit the cyclooxygenases at the highest concentration tested. All smoke condensate concentrations tested in the Salmonella/microsome assay induced mutation in both TA98 and TA100 in a dose dependent manner. A significant increase in the frequency of micronucleated cells, nucleoplasmic bridges and nuclear buds was observed in the cytome assay as well as in the % DNA damage in the comet assay.

    CONCLUSIONS: The findings indicated a dose dependent genotoxic potential of the smoke condensate in the bacterial and human C3A cells and may pose a health risk to women since the smoke bath is frequently practised. The study highlighted the need for further rigorous assessment of the risks associated with the smoke bath practice.

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