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14-Deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells

Tan HK, Muhammad TST, Tan ML

Toxicol Appl Pharmacol, 2016 06 01;300:55-69.
PMID: 27049118 DOI: 10.1016/j.taap.2016.03.017

14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells.
Transcriptional regulation of retinol binding protein 4 by Interleukin-6 via peroxisome proliferator-activated receptor α and CCAAT/Enhancer binding proteins

Mohd MA, Ahmad Norudin NA, Muhammad TST

Mol Cell Endocrinol, 2020 04 05;505:110702.
PMID: 31927097 DOI: 10.1016/j.mce.2020.110702

Interleukin-6 (IL-6) is a major mediator of the acute phase response (APR) that regulates the transcription of acute phase proteins (APPs) in the liver. During APR, the plasma levels of negative APPs including retinol binding protein 4 (RBP4) are reduced. Activation of the IL-6 receptor and subsequent signaling pathways leads to the activation of transcription factors, including peroxisome proliferator-activated receptor alpha (PPARα) and CCAAT/enhancer binding protein (C/EBP), which then modulate APP gene expression. The transcriptional regulation of RBP4 by IL-6 is not fully understood. Therefore, this study aimed to elucidate the molecular mechanisms of PPARα and C/EBP isoforms in mediating IL-6 regulation of RBP4 gene expression. IL-6 was shown to reduce the transcriptional activity of RBP4, and functional dissection of the RBP4 promoter further identified the cis-acting regulatory elements that are responsible in mediating the inhibitory effect of IL-6. The binding sites for PPARα and C/EBP present in the RBP4 promoter were predicted at -1079 bp to -1057 bp and -1460 bp to -1439 bp, respectively. The binding of PPARα and C/EBPs to their respective cis-acting elements may lead to antagonistic interactions that modulate the IL-6 regulation of RBP4 promoter activity. Therefore, this study proposed a new mechanism of interaction involving PPARα and different C/EBP isoforms. This interaction is necessary for the regulation of RBP4 gene expression in response to external stimuli, particularly IL-6, during physiological changes.
Lauric acid alleviates insulin resistance by improving mitochondrial biogenesis in THP-1 macrophages

Tham YY, Choo QC, Muhammad TST, Chew CH

Mol Biol Rep, 2020 Dec;47(12):9595-9607.
PMID: 33259010 DOI: 10.1007/s11033-020-06019-9

Mitochondrial dysfunction plays a crucial role in the central pathogenesis of insulin resistance and type 2 diabetes mellitus. Macrophages play important roles in the pathogenesis of insulin resistance. Lauric acid is a 12-carbon medium chain fatty acid (MCFA) found abundantly in coconut oil or palm kernel oil and it comes with multiple beneficial effects. This research objective was to uncover the effects of the lauric acid on glucose uptake, mitochondrial function and mitochondrial biogenesis in insulin-resistant macrophages. THP-1 monocytes were differentiated into macrophages and induce insulin resistance, before they were treated with increasing doses of lauric acid (5 μM, 10 μM, 20 μM, and 50 μM). Glucose uptake assay, cellular ROS and ATP production assays, mitochondrial content and membrane potential assay were carried out to analyse the effects of lauric acid on insulin resistance and mitochondrial biogenesis in the macrophages. Quantitative RT-PCR (qRT-PCR) and western blot analysis were also performed to determine the expression of the key regulators. Insulin-resistant macrophages showed lower glucose uptake, GLUT-1 and GLUT-3 expression, and increased hallmarks of mitochondrial dysfunction. Interestingly, lauric acid treatment upregulated glucose uptake, GLUT-1 and GLUT-3 expressions. The treatment also restored the mitochondrial biogenesis in the insulin-resistant macrophages by improving ATP production, oxygen consumption, mitochondrial content and potential, while it promoted the expression of mitochondrial biogenesis regulator genes such as TFAM, PGC-1α and PPAR-γ. We show here that lauric acid has the potential to improve insulin sensitivity and mitochondrial dysregulation in insulin-resistant macrophages.
Fulltext Induction of apoptosis and role of paclitaxel-loaded hyaluronic acid-crosslinked nanoparticles in the regulation of AKT and RhoA

Chaudhry GE, Akim A, Zafar MN, Abdullah MA, Sung YY, Muhammad TST

J Adv Pharm Technol Res, 2020 07 14;11(3):101-106.
PMID: 33102192 DOI: 10.4103/japtr.JAPTR_26_20

Cancer is a complex multifactorial disease and leading causes of death worldwide. Despite the development of many anticancer drugs, there is a reduced survival rate due to severe side effects. The nontargeted approach of convention drugs is one of the leading players in context to toxicity. Hyaluronan is a versatile bio-polymer and ligand of the receptor (CD44) on cancer cells. The MCF-7 and HT-29 cancer cell lines treated with hyaluronic acid-paclitaxel (HA-PTX) showed the distinguishing morphological features of apoptosis. Flow cytometric analysis showed that HA-PTX induces apoptosis as a significant mode of cell death. The activation level of tumor suppressor protein (p53) increased after PTX treatment in MCF-7, but no changes observed in HT-29 might be due to hereditary mutations. The lack of suppression in AKT and Rho A protein suggest the use of possible inhibitors in future studies which might could play a role in increasing the sensitivity of drug towards mutated cells line and reducing the possibilities for cancer cell survival, migration, and metastasis.
16-Hydroxycembra-1,3,7,11-tetraene, a new Cembrane Diterpene from Malaysian Soft Coral Genus Sarcophyton

Kamada T, Phan CS, Tin HS, Vairappan CS, Muhammad TST

Nat Prod Commun, 2016 Aug;11(8):1077-1078.
PMID: 30725560

One new cembrane diterpene, 16-hydroxycembra-1,3,7,11-tetraene (1), along with three known compounds, 15-hydroxycembra-1,3,7,11-tetraene (2), sarcophine (3) and sarcophytoxide (4) were isolated from Sarcophyton sp. collected from Karah Island, Terengganu, West Malaysia. Their structures were elucidated based on spectroscopic data. Activities of these compounds against antibacterial resistant clinical bacteria are reported. Only 1 exhibited inhibition against Staphylococcus aureus.
Fulltext Understanding Hyaluronan Receptor (CD44) Interaction, HA-CD44 Activated Potential Targets in Cancer Therapeutics

Chaudhry GE, Akim A, Naveed Zafar M, Safdar N, Sung YY, Muhammad TST

Adv Pharm Bull, 2021 May;11(3):426-438.
PMID: 34513617 DOI: 10.34172/apb.2021.050

Cancer is a complex mechanism involving a series of cellular events. The glycoproteins such as hyaluronan (HA) are a significant element of extracellular matrix (ECM), involve in the onset of cancer developmental process. The pivotal roles of HA in cancer progression depend on dysregulated expression in various cancer. HA, also gain attention due to consideration as a primary ligand of CD44 receptor. The CD44, complex transmembrane receptor protein, due to alternative splicing in the transcription process, various CD44 isoforms predominantly exist. The overexpression of distinct CD44 isoforms (CD44v) standard (CD44s) depends on the tumour type and stage. The receptor proteins, CD44 engage in a variety of biological processes, including cell growth, apoptosis, migration, and angiogenesis. HA-CD44 interaction trigger survival pathways that result in cell proliferation, invasion ultimately complex metastasis. The interaction and binding of ligand-receptor HA-CD44 regulate the downstream cytoskeleton pathways involve in cell survival or cell death. Thus, targeting HA, CD44 (variant and standard) isoform, and HA-CD44 binding consider as an attractive and useful approach towards cancer therapeutics. The use of various inhibitors of HA, hyaluronidases (HYALs), and utilizing targeted Nano-delivery of anticancer agents and antibodies against CD44, peptides gives promising results in vitro and in vivo. However, they are in clinical trials with favourable and unfavourable outcomes, which reflects the need for various modifications in targeting agents and a better understanding of potential targets in tumour progression pathways.
Fulltext In vitro and in vivo studies of nanoparticles of chitosan-Pandanus tectorius fruit extract as new alternative treatment for hypercholesterolemia via Scavenger Receptor Class B type 1 pathway

Oksal E, Pangestika I, Muhammad TST, Mohamad H, Amir H, Kassim MNI, et al.

Saudi Pharm J, 2020 Oct;28(10):1263-1275.
PMID: 33132720 DOI: 10.1016/j.jsps.2020.08.017

Pandanus tectorius fruit, a natural product rich in tangeretin and ethyl caffeate, has been reported to have potential as anti-hypercholesterolemia agent via Scavenger Receptor Class B type 1 (SR-B1) pathway. However, due to its semi-polar properties, P. tectorius extract exhibits poor solubility when used as a medical remedy. The extract's solubility can potentially be improved through a synthesis of nanoparticles of chitosan-P. tectorius fruit extract. This can also increase the extract's SR-B1 gene expression activity. To date, no studies of nanoparticles of chitosan-P. tectorius fruit extract and its pathway via SR-B1 have been published anywhere. In this study, cytotoxicity properties against HepG2 were explored by MTT. Then luciferase assay was used to detect their effectiveness in increasing SR-B1 activity. An in vivo study using Sprague dawley was carried out to observe the extract nanoparticles' effectiveness in reducing the cholesterol levels and the toxicity property in rat's liver. As the results showed, the extract nanoparticles had no cytotoxic activity against HepG2 cells and exhibited higher SR-B1 gene expression activity than the non-nanoparticle form. As the in vivo study proved, nanoparticle treatment can reduce the levels of TC (197%), LDL (360%), and TG (109%), as well as increase the level of HDL cholesterol by 150%, in comparison to those for the untreated high-cholesterol diet group. From the toxicity study, it was found that there was non-toxicity in the liver. It can be concluded that nanoparticles of chitosan-P. tectorius fruit extract successfully increased P. tectorius fruit extract's effectiveness in reducing hypercholesterolemia via SR-B1 pathway. Hence, it can be suggested that nanoparticles of chitosan-P. tectorius fruit extract is safe and suitable as an alternative treatment for controlling hypercholesterolemia via SR-B1 pathway.
Targeted drug delivery systems: synthesis and in vitro bioactivity and apoptosis studies of gemcitabine-carbon dot conjugates

Yunus U, Zulfiqar MA, Ajmal M, Bhatti MH, Chaudhry GE, Muhammad TST, et al.

Biomed Mater, 2020 09 26;15(6):065004.
PMID: 32442994 DOI: 10.1088/1748-605X/ab95e1

Gemcitabine (GEM) is used to treat various cancers such as breast, pancreatic, non-small lung, ovarian, bladder, and cervical cancers. GEM, however, has the problem of non-selectivity. Water-soluble, fluorescent, and mono-dispersed carbon dots (CDs) were fabricated by ultrasonication of sucrose. The CDs were further conjugated with GEM through amide linkage. The physical and morphological properties of these carbon dot-gemcitabine (CD-GEM) conjugates were determined using different analytical techniques. In vitro cytotoxicity and apoptosis studies of CD-GEM conjugates were evaluated by various bioactivity assays on human cell lines, MCF-7 (human breast adenocarcinoma), and HeLa (cervical cancer) cell lines. The results of kinetic studies have shown a maximum drug loading efficacy of 17.0 mg of GEM per 50.0 mg of CDs. The CDs were found biocompatible, and the CD-GEM conjugates exhibited excellent bioactivity and exerted potent cytotoxicity against tumor cells with an IC50 value of 19.50 μg ml-1 in HeLa cells, which is lower than the IC50 value of pure GEM (∼20.10 μg ml-1). In vitro studies on CD-GEM conjugates demonstrated the potential to replace the conventional administration of GEM. CD-GEM conjugates are more stable, have a higher aqueous solubility, and are more cytotoxic as compared to GEM alone. The CD-GEM conjugates show reduced side effects in the normal cells along with excellent cellular uptake. Hence, CD-GEM conjugates are more selective toward cancerous cell lines as compared to non-cancerous cells. Also, the CD-GEM conjugates successfully induced early and late apoptosis in cancer cell lines and might be effective and safe to use for in vivo applications.
Fulltext Vitex Rotundifolia Fractions Induced Apoptosis in Human Breast Cancer T-47D Cell Line via Activation of Extrinsic and Intrinsic Pathway

Chaudhry GE, Jan R, Naveed Zafar M, Mohammad H, Muhammad TST

Asian Pac J Cancer Prev, 2019 Dec 01;20(12):3555-3562.
PMID: 31870094 DOI: 10.31557/APJCP.2019.20.12.3555

OBJECTIVE: Breast cancer is the most frequently diagnosed cancer worldwide. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the extract and fractions of Vitex rotundifolia (leaves) in breast cancer cell line, T-47D.
METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.
RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of Bax and down-regulation of Bcl-2 protein. Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
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Antibacterial activity of hexane and methanol fractions of some selected plants against Klebsiella pneumoniae

Andriani Y, Hanifah W, Kholieqoh AH, Abdul Majid FA, Hermansyah H, Amir H, et al.

J Adv Pharm Technol Res, 2023;14(3):220-225.
PMID: 37692002 DOI: 10.4103/JAPTR.JAPTR_183_23

Besides adenovirus, pneumonia can also be caused by bacteria. One of the most common bacteria causing the pneumonia is Klebsiella pneumoniae. Currently, treatment by antibiotics has been widely used. Nevertheless, the increasing failure of existing antibiotics because of antibiotic resistance resulted by bacterial pathogens has become a serious problem to human health. Hence, there is a need for a new antibacterial potential agent against K. pneumoniae as an alternative treatment to the pneumonia to prevent the risk of a severe pneumonia for both healthy people and those already infected with the pneumonia. This study, therefore, investigated the antibacterial activity of some selected plants (Pandanus tectorius, Nypa fruticans, Sonneratia alba, Phaleria macrocarpa, Hibiscus tiliaceus, and Pongamia pinnata) against K. pneumoniae. In this study, samples were extracted successively by cold maceration using hexane and methanol. Antibacterial activity was determined by well and disc diffusion methods. Each fraction was prepared by two-fold dilutions from 20 mg/mL to 0.156 mg/mL. All data were analyzed in triplicate replication and presented as mean values ± standard deviation. Results showed that all methanol fractions of selected plants had antibacterial activity against K. pneumoniae, and well-diffusion method showed better antibacterial results compared to the agar well-diffusion method. The strongest activity was obtained by methanol fraction of S. alba leaf, followed by P. pinnata leaf, Nypa fruticans bark, H. tiliaceus leaf, P. macrocarpa leaf, and P. tectorius leaf with the minimum inhibitory concentrations (MICs) value between 0.625 and 5.0 mg/mL. Phytochemical screening revealed that all methanol fractions were rich in flavonoid content, which could have contributed to their antibacterial activity.
Corrigendum: Targeted drug delivery systems: synthesis andin vitrobioactivity and apoptosis studies of gemcitabine-carbon dot conjugates (2020Biomed. Mater.15065004)

Yunus U, Zulfiqar MA, Ajmal M, Bhatti MH, Chaudhry GE, Muhammad TST, et al.

Biomed Mater, 2023 Sep 01;18(5).
PMID: 37665183 DOI: 10.1088/1748-605X/acf358
Fulltext Natural Compound 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al from Momordica charantia Acts as PPARγ Ligand

Noruddin NAA, Hamzah MF, Rosman Z, Salin NH, Shu-Chien AC, Muhammad TST

Molecules, 2021 May 03;26(9).
PMID: 34063700 DOI: 10.3390/molecules26092682

Momordica charantia is a popular vegetable associated with effective complementary and alternative diabetes management in some parts of the world. However, the molecular mechanism is less commonly investigated. In this study, we investigated the association between a major cucurbitane triterpenoid isolated from M. charantia, 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al (THCB) and peroxisome proliferator activated receptor gamma (PPARγ) activation and its related activities using cell culture and molecular biology techniques. In this study, we report on both M. charantia fruit crude extract and THCB in driving the luciferase activity of Peroxisome Proliferator Response Element, associated with PPARγ activation. Other than that, THCB also induced adipocyte differentiation at far less intensity as compared to the full agonist rosiglitazone. In conjunction, THCB treatment on adipocytes also resulted in upregulation of PPAR gamma target genes expression; AP2, adiponectin, LPL and CD34 at a lower magnitude compared to rosiglitazone's induction. THCB also induced glucose uptake into muscle cells and the mechanism is via Glut4 translocation to the cell membrane. In conclusion, THCB acts as one of the many components in M. charantia to induce hypoglycaemic effect by acting as PPARγ ligand and inducing glucose uptake activity in the muscles by means of Glut4 translocation.
Effect of Gracilaria changii extract and its fraction in reverse cholesterol transport by targeting SR-BI gene

Rani MR, Azemi AK, Bakar K, Abu-Bakar L, Muhammad TST, Ismail N

Nat Prod Res, 2024 Mar 14.
PMID: 38486409 DOI: 10.1080/14786419.2024.2327851

This present study aimed to investigate the effects of Gracilaria changii (Red seaweed) extract and its fraction on scavenger receptor class B type I (SR-BI) gene expressions. In vitro studies of the activity of G. changii extract and its fraction against the therapeutic target for hypocholesterolemia were conducted using high-density lipoprotein (HDL) receptor SR-BI via luciferase assay in HepG2 cells. In the current study, methanol crude extract (MCE) and Fraction-2 of G. changii showed the highest expression levels of the SR-BI gene via luciferase assay and increased SR-BI mRNA expression compared to the negative control. Metabolite profiling of the MCE of G. changii by GC-MS revealed nine major compounds, comprising various fatty acids, particularly hexadecenoic acid. Therefore, the MCE and Fraction-2 of G. changii have the potential to be explored in the treatment of hypercholesterolaemia to prevent or reduce the severity of atherosclerosis development.
Fulltext Cancer and Disease Diagnosis - Biosensor as Potential Diagnostic Tool for Biomarker Detection

Chaudhry GE, Akim AM, Safdar N, Yasmin A, Begum S, Sung YY, et al.

J Adv Pharm Technol Res, 2022;13(4):243-247.
PMID: 36568055 DOI: 10.4103/japtr.japtr_106_22

Analysis of cancer biomarkers has enormous promise for advancing our molecular understanding of illness and facilitating more precise and timely diagnosis and follow-up care. MicroRNA, exosomes, ctDNA, CTCs, and proteins are only some of the circulating biomarkers that can be detected by liquid biopsy instead of the more intrusive and time-consuming process of doing a tissue biopsy. As the cancer diagnosis bio-markers reveal ultra-low levels in the early stages of the disease, highly sensitive approaches are urgently required. Researchers have taken an interest in a optical biosensor for detecting cancer biomarkers as a potential tool for early disease diagnosis. These techniques have the potential to aid in the development of effective treatments, ultimately leading to a higher rate of patient survival. This review briefly discuss the i) understanding of cancer and biomarkers for early diagonosis purpose ii) Molecular methods and ii) biosensor-based diagnostics. The reseach primary focus on advancement in biosensor design using various concepts ie., Electrochemical, Chemiluminescence and Colorimetric, Surface plasmons (SP), Surface plasmon resonance (SPR), localized surface plasmon resonance (LSPR), Fluorescence, Fiber-based sensors, Terahertz based biosensors, and Surface enhanced Raman spectroscopy (SERS). As a result of the local electric field amplification around plasmonic (usually gold and silver) nanostructures, surface-enhanced Raman spectroscopy (SERS) has emerged as a rapid, selective, and sensitive alternative to conventional laboratory analytical methods, making significant strides in a number of biosensing applications but still under developing stage to be used as diagnostic tool in clinical research.
Synthesis, characterization and anti-cancer properties of water-soluble bis(PYE) pro-ligands and derived palladium(ii) complexes

Zafar MN, Masood S, Chaudhry GE, Muhammad TST, Dalebrook AF, Nazar MF, et al.

Dalton Trans, 2019 Aug 08.
PMID: 31393494 DOI: 10.1039/c9dt01923e

The two cationic palladium(ii) complexes, [Pd(Len)2][OTf]2 (4) and [Pd(Lphen)2][OTf]2 (5), were synthesized by treatment of bis(benzonitrile)dichloropalladium(ii) with [H2Len][OTf]2 (2) or [H2Lphen][OTf]2 (3), respectively, in the presence of a weak base. The pro-ligands 2 and 3 were synthesized by melt reactions between N-methyl-4-chloropyridinium triflate (1) and the amines ethylenediamine or phenylenediamine, respectively. The water-soluble compounds 2-5 were fully characterized, including by single-crystal X-ray crystal structure determinations for 2-4. UV-Vis and fluorescence spectroscopy were used to study the binding interactions of 2-5 with CT-DNA. The spectroscopic data suggested the presence of intercalative and groove binding modes and this was supported by molecular docking studies. The in vitro cytotoxicity studies (IC50 values) showed that the human breast cancer cell lines MCF-7 and T47D were more sensitive towards 3, 4 and 5 than cisplatin. The cytotoxicity of the new compounds decreased in the order 5 > 4 > 3 > 2. Furthermore, the annexin V-FITC staining method strongly suggested the presence of phosphatidylserine (PS) on the outer membrane of the treated cells, which is a hallmark of apoptosis.
Fulltext Xylocarpus Moluccensis Induces Cytotoxicity in Human Hepatocellular Carcinoma HepG2 Cell Line via Activation of the Extrinsic Pathway

Chaudhry GE, Sohimi NKA, Mohamad H, Zafar MN, Ahmed A, Sung YY, et al.

Asian Pac J Cancer Prev, 2021 Feb 01;22(S1):17-24.
PMID: 33576208 DOI: 10.31557/APJCP.2021.22.S1.17

OBJECTIVE: Liver cancer is one of the most common causes of cancer death, with reduced survival rates. The development of new chemotherapeutic agents is essential to find effective cytotoxic drugs that give minimum side effects to the surrounding healthy tissues. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the crude and diethyl ether extract of Xylocarpus mouccensis on the human hepatocellular carcinoma cell line.
METHODS: The cytotoxicity activity was measured using the MTS assay. The mode of cell death determined by the apoptosis study, DNA fragmentation analysis done by using the TUNEL system. The pathway study or mechanism of apoptosis observed by study caspases 8, 9, 3/7 Glo-caspases method.
RESULTS: In this study, the methanol extracts prepared from leaf Xylocarpus mouccensis leaf produced cytotoxicity effect with IC50 (72hr) < 30µg/ml. The IC50 value at 72 hours exerted by diethyl ether extract of Xylocarpus moluccensis leaf was 0.22 µg/ml, which was more cytotoxic than to that of crude methanol extract. The results obtained by the colorimetric TUNEL system suggest that methanol crude extract of Xylocarpus moluccensis (leaf), diethyl ether extract of Xylocarpus moluccensis (leaf) and methanol extract of Xylocarpus granatum (bark) induced DNA fragmentation in the HepG2 cell line. Besides, the caspase-Glo assay demonstrated that diethyl ether leaf extract of Xylocarpus moluccensis triggered apoptotic cell death via activation of caspases -8, and -3/7 However, no visible activation was noticed for caspase -9. Furthermore, TLC indicates the presence of potential metabolites in an extract of Xylocarpus moluccensis.
CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in the extract of Xylocarpus moluccensis as a future therapeutic agent for the treatment of cancer.
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Fulltext Combined Multivariate Statistical Techniques and Water Quality Index (WQI) to Evaluate Spatial Variation in Water Quality

Begum S, Firdous S, Naeem Z, Chaudhry GE, Arshad S, Abid F, et al.

Trop Life Sci Res, 2023 Sep;34(3):129-149.
PMID: 37860095 DOI: 10.21315/tlsr2023.34.3.7

In present study, Water Quality Index (WQI) has been assessed of the Rawal Lake which is a major source of drinking water for people in the Federal Capital, Islamabad, and its adjacent city Rawalpindi in Pakistan. For this, the principal component analysis (PCA) and WQI were applied as an integrated approach to quantitatively explore difference based on spatial variation in 11 water quality parameters of the five major feeding tributaries of the Rawal Lake, Pakistan. The results of temperature in water, total dissolved solids, pH, electrical conductivity, chlorides and sulfates were well within the allowable World Health Organisation's (WHO) limits. However, the heavy metals like cadmium and lead were above permissible limits by the WHO in tributaries of Bari Imam and Rumli. Moreover, this has been proven by the Pearson correlation which suggested strong positive correlation (0.910*) between lead and cadmium. The results of present study were subjected to statistical analysis, i.e., PCA which gave three major factors contributing 96.5% of the total variance. For factor 1, pH, TDS, alkalinity, chlorides, sulfates and zinc have highest factor loading values (>0.60) and presented that these parameters were among the most significant parameters of first factor. As per the WQI results, the water was categorised in two major classes indicating that water of Bari Imam and Rumli is highly contaminated with heavy metals and totally unsuitable for drinking purposes. Based on the results of the present study, it is suggested to make heavy metals consideration as an integrated component in future planning for maintaining water quality of the Rawal Lake and its tributaries.
Fulltext Acute application of Centella asiatica extract enhanced AMPAR-mediated postsynaptic currents in rat entorhinal cortex

Wong JH, Reza F, Muthuraju S, Chuang HG, Zhang J, Senik MH, et al.

J Integr Neurosci, 2020 Jun 30;19(2):217-227.
PMID: 32706186 DOI: 10.31083/j.jin.2020.02.50

Centella asiatica is notable for its wide range of biological activities beneficial to human health, particularly its cognitive enhancement and neuroprotective effects. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are ionotropic glutamate receptors mediating fast excitatory neurotransmission essential in long-term potentiation widely thought to be the cellular mechanism of learning and memory. The method of whole-cell patch-clamp was used to study the effect of the acute application of Centella asiatica extract on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated spontaneous excitatory postsynaptic currents in the entorhinal cortex of rat brain slices. The respective low dose of test compounds significantly increased the amplitude of spontaneous excitatory postsynaptic currents while having no significant effects on the frequency. The findings suggested that Centella asiatica extract increased the response of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors at the postsynaptic level, revealing the potential role of Centella asiatica in modulating the glutamatergic responses in the entorhinal cortex of rat brain slices to produce cognitive enhancement effects.
Fulltext Antihypercholesterolemic and antiatherosclerotic potencies of Pandanus tectorius fruits via increasing scavenger receptor-B1 genes expression and inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity

Andriani Y, Chaudhry GE, Oksal E, Pangestika I, Ramli NM, Mohamad H, et al.

J Adv Pharm Technol Res, 2020 3 11;11(1):30-35.
PMID: 32154156 DOI: 10.4103/japtr.JAPTR_164_19

Atherosclerosis is a leading cause of death worldwide. The adverse side effects of currently available drugs urge to find more effective and safe remedial agents. Alternative candidates from natural resources are of great consequence in the emerging of new drugs. Pandanus tectorius (Pandanaceae) was traditionally used in Ayurvedic medicine to cure certain diseases. Thus, the current study conducted to elucidate the potency of P. tectorius fruit as antiatherosclerosis and antihypercholesterolemia agents through the regulation of high density lipoprotein (HDL) receptor (scavenger receptor [SR]-B1) gene expression and 3-hydroxy-3-methylglutaryl coenzyme A reductase reductase (HMGCR) in vitro, respectively. The P. tectorius fruit was noncytotoxic against the HepG2 cell line confirmed by 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyl tetrazolium bromide assay. The P. tectorius fruit successfully upregulates the SR-B1 gene expression and downregulate the HMGCR. Moreover, anin vivo study showed that P. tectorius has good activity on the upregulation of HDL and subsequently downregulation of total cholesterol level. Moreover, P. tectorius fruit did not show any increase in toxicity biomarkers serum glutamic oxaloacetic transaminase and serum glutamate pyruvate transaminase in vivo. These results found that P. tectorius fruits have potency as the preventive agent for hypercholesterolemia and atherosclerosis via SR-B1 and HMGCR mechanisms of action.
Pd(II) complexes with chelating N-(1-alkylpyridin-4(1H)-ylidene)amide (PYA) ligands: Synthesis, characterization and evaluation of anticancer activity

Zafar MN, Butt AM, Chaudhry GE, Perveen F, Nazar MF, Masood S, et al.

J Inorg Biochem, 2021 11;224:111590.
PMID: 34507110 DOI: 10.1016/j.jinorgbio.2021.111590

The bidentate N-(1-Alkylpyridin-4(1H)-ylidene)amide (PYA) pro-ligands [H2LBn][Cl]2 (2), and [H2LMe][TfO]2 (3) were prepared by simple alkylation reactions of the known compound, N,N-di(pyridin-4-yl)oxalamide (H2L, 1). The Pd(II) complexes, [Pd(LBn)2][Cl]2 (4), [Pd(LMe)2][Cl][TfO] (5), Pd(LBn)Cl2 (6) and Pd(LMe)Cl2 (7) were synthesized through reactions between these pro-ligands and suitable Pd(II) substrates in the presence of base. The molecular structures of 3 and 6 were obtained by single crystal X-ray structure determinations. Studies of the experimental and computational DNA binding interactions of the compounds 1-7 revealed that overall 4 and 6 have the largest values for the binding parameters Kb and ΔGbo. The results showed a good correlation with the steric and electronic parameters obtained by quantitative structure activity relationship (QSAR) studies. In-vitro cytotoxicity studies against four different cell lines showed that the human breast cancer cell lines MCF-7, T47D and cervical cancer cell line HeLa had either higher or similar sensitivities towards 4, 6 and 2, respectively, compared to cisplatin. In general, the cytotoxicity of the compounds, represented by IC50 values, decreased in the order 4 > 6 > 2 > 5 > 3 > 1 > 7 in cancer cell lines. Apoptosis contributed significantly to the cytotoxic effects of these anticancer agents as evaluated by apoptosis studies.

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