Asian Pacific Journal of Tropical Biomedicine

375-384

Authors: Sivakumar Allur Subramaniyan, Naziya Begum, Sung Jae Kim, Youn Hee Choi, Taek-Jeong Nam

Pyropia yezoensis (P. yezoensis) is a popular species of red algae that are commercially cultivated and consumed in East Asia, China, Japan, and Korea. The high protein content of P. yezoensis provides a source of multiple bioactive peptides exhibiting antioxidant, anti-inflammatory, antihypertensive, anticancer, tissue healing, immunomodulatory, and anticoagulant properties. Furthermore, many other biologically active substances in P. yezoensis, including carbohydrates, lipids, dietary fibers, and polyphenols, have shown potential health benefits and are important in both the food and agriculture industries. This review provides a detailed summary of researches over the last decade on the biological and medicinal properties of bioactive peptides. The information was extracted from various electronic resources, including Google Scholar, PubMed, MEDLINE, and Google Patents.

394-404

Authors: Muhammad Furqan Akhtar, Arsalan Shagufta, Ammara Saleem, Mirza Muhammad Faran Ashraf Baig, Ali Sharif, Azhar Rasul, Mohamed M Abdel-Daim

Objective: To evaluate the antidiabetic potential of leaf extracts of Tylophora hirsuta (T. hirsuta). Methods: The methanolic and ethyl acetate extracts of T. hirsuta leaves were analyzed by high pressure liquid chromatography. In vitro antioxidant activity was determined by ferric ion reduction, 1, 1-diphenyl-2-picrylhydrazyl, and hydrogen peroxide scavenging methods. In vitro alpha amylase (α-amylase) inhibitory activity of the plant extracts was assessed. In vivo antidiabetic potential was determined in alloxan-induced diabetic mice to assess glycated hemoglobin (HbA1c), oral glucose tolerance, serum amylase, lipid profile, fasting blood glucose, and body weight. Histopathological lesions of the pancreas, liver and kidney were observed. Oxidative stress biomarkers such as superoxide dismutase, catalase and peroxidase were also determined. Results: Quercetin, chlorogenic acid, p-coumaric acid, and m-coumaric acid were found in the plant extracts. The methanolic plant extract exhibited higher in vitro antioxidant activities than the ethyl acetate extract. Moreover, methanolic plant extract exhibited (83.90±1.56)% α-amylase inhibitory activity at 3.2 mg/ mL concentration. Animal study showed that the methanolic extract of T. hirsuta improved the levels of fasting blood glucose, HbA1c, serum α-amylase, lipid profile, liver function biomarkers, and kidney functions of diabetic mice. Moreover, the methanolic extract ameliorated diabetes-related oxidative stress by increasing superoxide dismutase and catalase activities and decreasing peroxidase and malondialdehyde levels. Histopathological examination showed that the plant extract had improved the integrity of pancreatic islets of Langerhans and reduced the pathological lesions in the liver and kidney of diabetic mice. Conclusions: The methanolic extract of T. hirsuta exhibits pronounced antidiabetic activity in mice through reduction of oxidative stress. The plant extract has several natural antioxidants such as phenolic acids. T. hirsuta extract could serve as a nutraceutical for managing diabetes mellitus.

414-420

Authors: Ahmed Nafis, Fatima El Khalloufi, Asmae Aknaf, Brahim Oudra, Najat Marraiki, Sarah Al-Rashed, Abdallah M Elgorban, Asad Syed, Lahcen Hassani, Luísa Custódio

Objective: To study the chemical profile, antimicrobial properties, and synergistic effect with known antibiotics of essential oil extracted from the marine red macroalgae Centroceras clavulatum (C. Agardh) Montagne, collected in Morocco. Methods: The chemical composition of the oil was analyzed by gas chromatography-mass spectrometry. The oil was evaluated for antibacterial (Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Micrococcus luteus, Staphylococcus aureus, and Klebsiella pneumoniae), and antifungal activity (Candida albicans, Candida glabrata, Candida krusei, and Candida parapsilosis), by the disc diffusion method. The minimum inhibitory and minimum microbicidal concentrations of the oil were determined, as well as the synergistic effects of its application combined with the antibiotics ciprofloxacin and fluconazole, by the checkerboard method. Results: Thirty molecules were identified in the essential oil, comprising 96.27% of the total oil composition. Monoterpenes such as carvacrol (36.06%) were the most abundant compounds, followed by caryophyllene (14.67%), endo-borneol (9.04%), pyroterebic acid (3.23%) and caryophyllene oxide (3.13%). The oil exhibited a moderate antimicrobial activity with inhibition zone diameters ranging from 9.0 to 15.0 mm. The minimum inhibitory concentration values varied between 0.9 and 14.7 mg/mL, and Bacillus subtilis and Escherichia coli were the more sensitive bacteria with 0.9 and 1.9 mg/mL, respectively. The minimum microbicidal concentration values ranged from 0.4 to 14.7 mg/mL. A significant synergic action was observed when the oil was applied in combination with ciprofloxacin and fluconazole, with fractional inhibitory concentration index values ranging from 0.31 to 0.50. Synergy was found in 80% of the combinations and a 2 to 16-fold reduction of antibiotics MIC was observed. Conclusions: Our findings suggest that the essential oil of Centroceras clavulatum should be further appraised for its potential use in the management of multi-drug resistant microorganisms, with the purpose to restore the activity of standard antimicrobial drugs.

327-334

Authors: Mohammad Reza Khazdair, Akbar Anaeigoudari, Gabriel A Agbor

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a novel coronavirus identified at the end of 2019. It is recognized as the causative agent of coronavirus disease 2019 (COVID-19). Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19. The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2. The Web of Science, PubMed, Scopus, and Google Scholar were searched using keywords: “COVID-19”, “SARS-CoV-2”, “Kaempferol” and “Quercetin” in the Title/Abstract. Relevant published articles in the English language until August 2020 were considered. Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel (3a channel) expressed in SARS-CoV infected cells. They also reduced the level of reactive oxygen species, expression of inducible nitric oxide synthase, pro-inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-6, IL-10, and IL-12 p70, and chemokines. Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral, antioxidant, anti-inflammatory, and immunomodulatory effects.

344-352

Authors: Saber Mohamed Eweda, Mennatallah Ahmed Ali, Hala Mohamed Abd El-Bary, Nahed Hussein El-Sokkary, Madiha Hassan Helmy, Maher Abdel-Nabi Kamel

Objective: To investigate the modulatory effects of bitter gourd extract on the insulin signaling pathway in the liver and skeletal muscle tissues of diabetic rats. Methods: The ethanolic extract of bitter gourd was prepared and its contents of total polyphenols and flavonoids were assayed. A neonatal streptozotocin-induced diabetic rat model was established and the diabetic rats were assigned into different groups and were treated with different doses of bitter gourd extract (100, 200, 400, or 600 mg/kg) or with glibenclamide (0.1 mg/kg) for 30 d. Fasting blood glucose, insulin, and lipid profile were evaluated and the insulin signaling pathway in the liver and skeletal muscle of rats was investigated. The correlations between homeostasis model assessment (HOMA) and the components of insulin signaling pathway were also evaluated. Results: Different doses of bitter gourd extract significantly ameliorated fasting blood glucose level and HOMA index for insulin resistance. Moreover, bitter gourd extract increased serum insulin and improved disrupted serum lipid profile. The levels of insulin receptor substrate-1 (IRS-1), p-insulin receptor β (p-IR-β), protein kinase C (PKC), GLUT2, and GLUT4 were improved by treatment with bitter gourd extract. The best results were obtained with 400 mg/kg dose of the extract, the effect of which was equivalent to that of glibenclamide. HOMA in the bitter gourd treated rats was negatively correlated with p-IR-β, IRS-1 and PKC in hepatic and skeletal muscle. HOMA was also negatively correlated with skeletal muscle GLUT4. Conclusions: Bitter gourd extract improves glucose homeostasis and lipid profile in diabetic rats via enhancement of insulin secretion and sensitivity. Therefore, bitter gourd can be used as a potential pharmacological agent for the treatment of type 2 diabetes mellitus.

363-374

Authors: Anish Nag, Ritesh Banerjee, Priya Goswami, Maumita Bandyopadhyay, Anita Mukherjee

Objective: To compare the antioxidant and anti-genotoxic properties of Alpinia (A.) galanga, Curcuma (C.) amada, and C. caesia. Methods: Cytotoxicity of ethanolic extracts of A. galanga, C. amada, and C. caesia at selected doses was evaluated by trypan blue, MTT, and flow cytometry-based assays. Genotoxicity and anti-genotoxicity (against methyl methanesulfonate, 35 μM and H2O2, 250 μM) of these plants were studied by comet assay in human lymphocytes in vitro. Furthermore, DPPH, ABTS, FRAP, lipid peroxidation, and hydroxyl radical scavenging assays were performed to study the antioxidant potentials of the plants. Finally, anti-genotoxic potential of C. amada was validated in Swiss albino mice using comet assay. Phytochemical composition of C. amada was determined by GC/MS and HPLC. Results: The selected doses (2.5, 5, and 10 μg/mL) of A. galanga, C. amada, and C. caesia were non-toxic by cytotoxicity tests. All three ethanolic extracts of plant rhizomes demonstrated antioxidant and anti-genotoxic properties against methyl methanesulfonate-and H2O2-induced oxidative stress in human peripheral blood lymphocytes in vitro. Multivariate analysis revealed that various antioxidant properties of these extracts in DPPH, ABTS, and FRAP assays were strongly correlated with their total phenolic constituents. C. amada extract conferred protection against cyclophosphamide-induced DNA damage in the bone marrow cells of mice and DNA damage was significantly inhibited by 2.5 mg/kg C. amada extract. Conclusions: C. amada is rich in potentially bioactive molecules and exhibits potent antioxidant activities. Its anti-genotoxicity against cyclophosphamide-induced oxidative stress is also confirmed in this study.

285-297

Authors: Heba M.I. Abdallah

Acute kidney injury, previously known as acute renal failure (AKI), is defined as an abrupt decrease in kidney function that occurs within hours or days. This new nomenclature opens a new door for possibility of treatment of developing renal injury before progression to unresolved renal failure. AKI arises due to diverse etiologic factors that rely mainly on three categories namely, pre-renal, intrinsic renal, and post-renal factors with different clinical pictures, and confers a spectrum of injury ranging from mild to severe and sometimes leads to end-stage renal disease. Complexity of pathogenesis and other factors generate barriers to developing effective treatments despite a large number of experimental and clinical studies. In this review, recent advances in the potential of the currently used drugs for renoprotection, novel pharmacological targets, and prospective therapeutics for AKI are discussed. The information in this review was extracted from electronic resources (PubMed, Google Scholar, Wiley, Science Direct, Springer), and English scientific books by using keywords including kidney, injury, recent therapy, and pharmacological targets. The articles were carefully checked for their relevance to the current manuscript. Recent targets of cellular repair or regenerative processes involved in AKI such as autophagy, ferroptosis inhibition, and p53 antagonism seem to be effective in disease control. This may help researchers and clinicians to understand how to target the interrelated molecular and cellular mechanisms underlying the pathogenesis of AKI.

308-316

Authors: Reem Al Monla, Yahya Salma, Achraf Kouzayha, Hala Gali-Muhtasib, Zeina Dassouki, Hiba Mawlawi

Objective: To investigate the antioxidant and cytotoxic properties of the most active extracts from Ulva lactuca and Laurencia obtusa against colon and cervical cancer cell lines. Methods: The antioxidant radical scavenging activity of the algal extracts was estimated using the 2,2-diphenyl-1-picrylhydrazyl colorimetric assay. Moreover, the cytotoxic potential of these bioactive extracts was studied against HCT-116 and HeLa cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing analysis was adopted to evaluate the anti-metastatic effects of protein extracts from both algae. Cell cycle analysis was performed by flow cytometry, and apoptotic bodies were detected using 4’,6-diamidino-2-phenylindole fluorescent staining. Amino acids of hydrolyzed protein extract were separated and identified chromatographically by high performance liquid chromatography. Results: The green algae Ulva lactuca had higher lipid content than Laurencia obtusa, whereas the latter had higher protein content with high antioxidant capacity. Protein extracts had significant dose- and time-dependent cytotoxicity and anti-metastatic activity against HCT-116 cells. Protein b extracts of both algae obtained from the chloroform:hexane solvent lipid-free residue caused morphological changes and induced apoptosis of HCT-116 cells. Further analysis revealed that apoptosis induced upon Laurencia obtusa protein b treatment was triggered via the ROS pathway, causing a significant increase in the sub-G1 population. Glycine and arginine (5.94 and 5.47 μM, respectively) were the most common amino acids in Laurencia obtusa protein b extract. Conclusions: Proteins of Laurencia obtusa and Ulva lactuca could be considered as an adjuvant nutraceutical source of pro-apoptotic and anti-metastatic biomolecules against colon cancer.

231-243

Authors: Arnica F Lal, Shaminder Singh, Francisco C Franco, Sonam Bhatia

Polyphenols are the secondary metabolic products of plants and are considered as active constituents to possess therapeutic effects. To date, a vast number of scientific literature addressed the potential of polyphenols as bio-efficient compounds owing to their structural diversity. Due to the presence of several hydroxyl groups, they are metabolized quickly due to conjugation reaction and thus, readily produce toxic metabolites as a defense material against many pathogens, reflecting their safety strategy. This review focuses on the anti-quorum sensing and biofilm inhibition activity of polyphenols, which display their potential to treat bacterial infections by combating the virulence caused by pathogenic agents. Thus, for mitigating quorum sensing-controlled pathogenesis, the use of polyphenol-based phytochemicals holds immense potential to cure infections. The application of polyphenol as sensitizing agent/ adjuvant therapeutics which act in synergism with antibiotics is highly remarkable.

254-262

Authors: Raghda A El-Sayed, Fatma M El-Demerdash, Mohammed A El-Magd

Objective: To investigate the protective and therapeutic role of ginseng against silicon dioxide nanoparticles (SiO2NPs)-induced toxicity in the lungs. Methods: Sixty male rats were divided into five groups (n = 12/ group); group 1 was used as a control, group 2 received ginseng, group 3 was treated with SiO2NPs, and group 4 was pretreated with ginseng one week before SiO2NPs, while group 5 was given SiO2NPs one week before supplementation with ginseng. Animals were treated with both ginseng and SiO2NPs orally for five weeks. Real-time PCR was used to measure gene expression. Besides, DNA damage and cell cycle changes were determined by comet assay and flow cytometry, respectively. Histological study was also done to assess the effect of ginseng on SiO2NPs-induced toxicity. Results: SiO2NPs increased lipid peroxidation and decreased the activities of antioxidant enzymes. SiO2NPs induced apoptosis in lung tissues as revealed by upregulation of Bax and caspase 3 and downregulation of Bcl-2 as well as the induction of DNA damage. SiO2NPs also caused inflammation as indicated by upregulation of the inflammation-related genes [interleukin 1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX2), and transforming growth factor-beta 1 (TGFβ1)] as well as cell cycle arrest in the G0/G1 phase of lung cells. Moreover, histopathological examination proved the biochemical and molecular perturbations that occurred due to SiO2NPs toxicity. However, ginseng alleviated SiO2NPs-induced toxicity in rat lung. Conclusions: Ginseng has a potent preventive and therapeutic effect and could be used in the treatment of SiO2NPs-induced pulmonary toxicity.

273-284

Authors: Li-Shan Yan, Li Wang, Brian Chi-Yan Cheng, Yu Ding, Jing Kong, Qing Gao Wang, Xiu-Qiong Fu, Shuo-Feng Zhang, Gan Luo, Yi Zhang

Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.

183-193

Authors: Ketmanee Senaphan, Upa Kukongviriyapan, Pisit Suwannachot, Geerasak Thiratanaboon, Weerapon Sangartit, Supawan Thawornchinsombut, Akkasit Jongjareonrak

Objective: To examine the ameliorative effect of rice bran hydrolysates (RBH) on metabolic disorders, cardiac oxidative stress, heart rate variability (HRV), and cardiac structural changes in high fat and high fructose (HFHF)-fed rats. Methods: Male Sprague-Dawley rats were daily fed either standard chow diet with tap water or an HFHF diet with 10% fructose in drinking water over 16 weeks. RBH (500 and 1 000 mg/kg/day) was orally administered to the HFHF-diet-fed rats during the last 6 weeks of the study period. At the end of the treatment, metabolic parameters, oxidative stress, HRV, and cardiac structural changes were examined. Results: RBH administration significantly ameliorated metabolic disorders by improving lipid profiles, insulin sensitivity, and hemodynamic parameters. Moreover, RBH restored HRV, as evidenced by decreasing the ratio of low-frequency to high-frequency power of HRV, a marker of autonomic imbalance. Cardiac oxidative stress was also mitigated after RBH supplementation by decreasing cardiac malondialdehyde and protein carbonyl, upregulating eNOS expression, and increasing catalase activity in the heart. Furthermore, RBH mitigated cardiac structural changes by reducing cardiac hypertrophy and myocardial fibrosis in HFHF-diet-fed rats. Conclusions: The present findings suggest that consumption of RBH may exert cardioprotective effects against autonomic imbalances, cardiac oxidative stress, and structural changes in metabolic syndrome.

205-213

Authors: Aarti S Kale, Avinash R Wadkar, Umesh B Mahajan, Lalit A Birari, Sateesh Belemkar, Sameer N Goyal, Shreesh Ojha, Sanjay J Surana, Chandragouda R Patil, Kalpesh R Patil

Objective: To investigate the effect of aloin against chronic constriction injury (CCI)-induced neuropathic pain in rats. Methods: Rats were randomly divided into 7 groups: Group I (normal control), Group II (sham-operated), Group III (CCI control) and Group IV, V, VI, and VII, which underwent CCI surgery and then were administered with aloin (5 mg/kg, p.o.; 25 mg/kg, p.o.; 125 mg/kg, p.o.) and gabapentin (50 mg/kg, p.o.), respectively for 14 days. Peripheral neuropathy was induced by silk ligatures (4-0) loosely placed around the sciatic nerve. Nociceptive thresholds against mechanical stimuli (Von-Frey filaments) and thermal stimuli (12 °C and 40 °C) were measured at mid-plantar paw region ipsilateral to the compressed nerve on day-3, 7, 11, and 14. The concentration of cytokines including tumor necrosis factor-α (TNF-α), interleukin-6, and interleukin-1β was estimated at day-7. At day 14, motor nerve conduction velocity was determined under urethane anesthesia (1.25 g/kg). Oxidative stress parameters (malondiadehyde, glutathione, catalase, and superoxide dismutase) were estimated in sciatic nerve homogenates at day 14. Representative nerve samples were processed for histological investigations. Results: Aloin significantly reduced CCI-induced mechanical and thermal allodynia. It also improved motor nerve conduction velocity and decreased oxidative stress in nerve tissues. In addition, it decreased pro-inflammatory cytokine levels and restored the histoarchitecture of compressed sciatic nerve. Conclusions: Aloin mitigates CCI-induced neuropathic pain in rats by inhibiting oxidative stress and pro-inflammatory cytokines in the afflicted sciatic nerve.

222-230

Authors: Yung Hyun Choi

Objective: To investigate the effect of honokiol on oxidative damage in HaCaT human keratinocytes. Methods: HaCaT cells were exposed to hydrogen peroxide (H2O2), following pretreatment with various concentrations of honokiol. The alleviating effects of honokiol on HaCaT cell viability and cell death, reactive oxygen species (ROS) production, DNA damage, mitochondrial dynamics, and inhibition of adenosine triphoaphate production against H2O2 were investigated. Western blotting analysis was used to analyze the expression levels of specific proteins. Results: Honokiol suppressed H2O2-induced cytotoxicity and DNA damage by blocking abnormal ROS accumulation. Honokiol also prevented apoptosis by inhibiting loss of mitochondrial membrane potential and release of cytochrome c from the mitochondria into the cytosol, decreasing the Bax/Bcl-2 ratio, and reducing the activity of caspase-3 in H2O2-stimulated HaCaT cells. In addition, honokiol attenuated H2O2-induced reduction of adenosine triphosphate content, and activation of AMP-activated protein kinase (AMPK) was markedly promoted by honokiol in H2O2-stimulated cells. Importantly, the anti-apoptosis and anti-proliferative activity of honokiol against H2O2 was further enhanced by adding an activator of AMPK, indicating that honokiol activated AMPK in HaCaT keratinocytes to protect against oxidative damage. Conclusions: The present results indicate that honokiol may be useful as a potential therapeutic agent against various oxidative stress-related skin diseases.