Displaying publications 1 - 20 of 28 in total

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  1. Zakaria ZA, Safarul M, Valsala R, Sulaiman MR, Fatimah CA, Somchit MN, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2005 Jul;372(1):55-62.
    PMID: 16133487
    A series of preliminary studies was carried out to evaluate the antinociceptive (pain relief) activity of the aqueous extract of Corchorus olitorius L. leaves (COAE) and to determine the influence of temperature and opioid receptors on COAE activity using the abdominal constriction and hot plate tests in mice. COAE, at concentrations of 10, 25, 50, 75, and 100%, showed both peripheral and central antinociception that are non-concentration- and concentration-dependent respectively. The peripheral activity was clearly observed at a concentration of 25% and diminished at a concentration of 100%, while the central activity was observed at all the concentrations of COAE used. Furthermore, the insignificant results obtained indicated that this peripheral activity (at concentrations of 25 and 50%) was comparable to that of morphine (0.8 mg/kg). Pre-heating COAE at a temperature of 80 degrees C and 100 degrees C, or 60 degrees C and 80 degrees C was found to enhance its peripheral and central antinociception respectively. Pre-treatment with naloxone (10 mg/kg), a general opioid receptor antagonist, for 5 min, followed by COAE, was found to completely block its peripheral, but not central, antinociceptive activity. Based on this observation, we conclude that the antinociceptive activity exhibited by C. olitorius is enhanced by the increase in temperature and may be mediated peripherally, but not centrally, at least in part, via an opioid receptor.
  2. Yew KC, Tan QR, Lim PC, Low WY, Lee CY
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1421-1431.
    PMID: 37728622 DOI: 10.1007/s00210-023-02716-x
    Direct-acting antivirals (DAA) have become the treatment of choice for hepatitis C. Nevertheless, efficacy of DAA in preventing hepatitis C complications remains uncertain. We evaluated the impact of DAA on hepatocellular carcinoma (HCC) occurrence and recurrence, all-cause mortality, liver decompensation and liver transplantation as compared to non-DAA treated hepatitis C and the association to baseline liver status. A systematic search for articles from March 1993 to March 2022 was conducted using three electronic databases. Randomized, case-control and cohort studies with comparison to non-DAA treatment and reporting at least one outcome were included. Meta-analysis and sub-group meta-analysis based on baseline liver status were performed. Of 1497 articles retrieved, 19 studies were included, comprising of 266,310 patients (56.07% male). DAA reduced HCC occurrence significantly in non-cirrhosis (RR 0.80, 95% CI 0.69-0.92) and cirrhosis (RR 0.39, 95% CI 0.24-0.64) but not in decompensated cirrhosis. DAA treatment lowered HCC recurrence (RR 0.71, 95% CI 0.55-0.92) especially in patients with baseline HCC and waiting for liver transplant. DAA also reduced all-cause mortality (RR 0.43, 95% CI 0.23-0.78) and liver decompensation (RR 0.52, 95% CI 0.33-0.83) significantly. However, DAA did not prevent liver transplantation. The study highlighted the importance of early DAA initiation in hepatitis C treatment for benefits beyond sustained virological response. DAA therapy prevented HCC particularly in non-cirrhosis and compensated cirrhosis groups indicating benefits in preventing further worsening of liver status. Starting DAA early also reduced HCC recurrence, liver decompensation, and all-cause mortality.
  3. Tan JR, Chakravarthi S, Judson JP, Haleagrahara N, Segarra I
    Naunyn Schmiedebergs Arch Pharmacol, 2013 Jul;386(7):619-33.
    PMID: 23552887 DOI: 10.1007/s00210-013-0861-4
    Sunitinib is a tyrosine kinase inhibitor for GIST and advanced renal cell carcinoma. Diclofenac is used in cancer pain management. Coadministration may mediate P450 toxicity. We evaluate their interaction, assessing biomarkers ALT, AST, BUN, creatinine, and histopathological changes in the liver, kidney, heart, brain, and spleen. ICR mice (male, n = 6 per group/dose) were administered saline (group A) or 30 mg/kg diclofenac ip (group B), or sunitinib po at 25, 50, 80, 100, 140 mg/kg (group C) or combination of diclofenac (30 mg/kg, ip) and sunitinib (25, 50, 80, 100, 140 mg/kg po). Diclofenac was administered 15 min before sunitinib, mice were euthanized 4 h post-sunitinib dose, and biomarkers and tissue histopathology were assessed. AST was 92.2 ± 8.0 U/L in group A and 159.7 ± 14.6 U/L in group B (p < 0.05); in group C, it the range was 105.1-152.6 U/L, and in group D, it was 156.0-209.5 U/L (p < 0.05). ALT was 48.9 ± 1.6 U/L (group A), 95.1 ± 4.5 U/L (p < 0.05) in group B, and 50.5-77.5 U/L in group C and 82.3-115.6 U/L after coadministration (p < 0.05). Renal function biomarker BUN was 16.3 ± 0.6 mg/dl (group A) and increased to 29.9 ± 2.6 mg/dl in group B (p < 0.05) and it the range was 19.1-33.3 mg/dl (p < 0.05) and 26.9-40.8 mg/dl in groups C and D, respectively. Creatinine was 5.9 pmol/ml in group A; 6.2 pmol/ml in group B (p < 0.01), and the range was 6.0-6.2 and 6.2-6.4 pmol/ml in groups C and D, respectively (p < 0.05 for D). Histopathological assessment (vascular and inflammation damages) showed toxicity in group B (p < 0.05) and mild toxicity in group C. Damage was significantly lesser in group D than group B (p < 0.05). Spleen only showed toxicity after coadministration. These results suggest vascular and inflammation protective effects of sunitinib, not shown after biomarker analysis.
  4. Tan CS, Yam MF
    Naunyn Schmiedebergs Arch Pharmacol, 2018 06;391(6):561-569.
    PMID: 29552696 DOI: 10.1007/s00210-018-1481-9
    Previous studies have demonstrated that 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF) content in Orthosiphon stamineus fractions correlate with its vasorelaxation activity. Even with the availability of previous studies, there is still very little information on the vasorelaxation effect of TMF, and few scientific studies have been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of the TMF. The vasorelaxation activity and the underlying mechanisms of TMF were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. TMF caused the relaxation of aortic rings with endothelium pre-contracted with phenylephrine. However, the vasorelaxant effect of TMF was significantly decreased in PE-primed endothelium-denuded and potassium chloride-primed endothelium-intact aortic rings. In the presence of Nω-nitro-L-arginine methyl ester, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, indomethacin, tetraethylammonium, 4-aminopyridine, barium chloride, atropine and propranolol, the relaxation stimulated by TMF was significantly reduced. TMF was also found to reduce Ca2+ release from sarcoplasmic reticulum (via IP3R) and block calcium channels (VOCC). The present study demonstrates the vasorelaxant effect of TMF involves NO/sGC/cGMP and prostacyclin pathways, calcium and potassium channels and muscarinic and beta-adrenergic receptors.
  5. Siaw YM, Jeevanandam J, Hii YS, Chan YS
    Naunyn Schmiedebergs Arch Pharmacol, 2020 Dec;393(12):2253-2264.
    PMID: 32632566 DOI: 10.1007/s00210-020-01934-x
    In recent times, magnesium oxide (MgO) nanoparticles are proven to be an excellent antibacterial agent which inhibits the growth of bacteria by generating reactive oxygen species (ROS). Release of ROS by nanoparticles will damage the cell membrane of bacteria and leads to the leakage of bacterial internal components and cell death. However, chemically synthesized MgO nanoparticles may possess toxic functional groups which may inhibit healthy human cells along with bacterial cells. Thus, the aim of the present study is to synthesize MgO nanoparticles using leaf extracts of Amaranthus tricolor and photo-irradiation of visible light as a catalyst, without addition of any chemicals. Optimization was performed using Box-Behnken design (BBD) to obtain the optimum condition required to synthesize smallest nanoparticles. The parameters such as time of reaction, the concentration of precursor, and light intensity have been identified to affect the size of biosynthesized nanoparticles and was optimized. The experiment performed with optimized conditions such as 0.001 M concentration of magnesium acetate as precursor, 5 cm distance of light (intensity), and 15 min of reaction time (light exposure) has led to the formation of 74.6 nm sized MgO nanoparticles. The antibacterial activities of MgO nanoparticles formed via photo-irradiation and conventional biosynthesis approach were investigated and compared. The lethal dosage of E. coli for photo-irradiated and conventional biosynthesis MgO nanoparticles was 0.6 ml and 0.4 ml, respectively. Likewise, the lethal dosage of S. aureus for both biosynthesis approaches was found to be 0.4 ml. The results revealed that the antibacterial activity of MgO nanoparticles from both biosynthesis approaches was similar. Thus, photo-irradiated MgO nanoparticles were beneficial over heat-mediated conventional method due to the reduced synthesis duration.
  6. Sadikan MZ, Abdul Nasir NA
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3395-3406.
    PMID: 37401966 DOI: 10.1007/s00210-023-02599-y
    Diabetic retinopathy (DR) is one of the leading causes of permanent central blindness worldwide. Despite the complexity and inadequate understanding of DR pathogenesis, many of the underlying pathways are currently partially understood and may offer potential targets for future treatments. Anti-VEGF medications are currently the main medication for this problem. This article provides an overview of the established pharmacological treatments and those that are being developed to cure DR. We firstly reviewed the widely utilized approaches including pan-retinal photocoagulation therapy, anti-VEGF therapy, corticosteroid therapy, and surgical management of DR. Next, we discussed the mechanisms of action and prospective benefits of novel candidate medications. Current management are far from being a perfect treatment for DR, despite mild-term favorable efficiency and safety profiles. Pharmacological research should work toward developing longer-lasting treatments or new drug delivery systems, as well as on identifying new molecular targets in the pathogenetical mechanism for DR. In order to find a treatment that is specifically designed for each patient, it is also necessary to properly characterize patients, taking into account elements like hereditary factors and intraretinal neovascularization stages for effective utilization of drugs. The current and potential approaches for diabetic retinopathy. Image was constructed using Biorender.com.
  7. Rusli N, Amanah A, Kaur G, Adenan MI, Sulaiman SF, Wahab HA, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2019 04;392(4):481-496.
    PMID: 30604191 DOI: 10.1007/s00210-018-01605-y
    Mitragynine is a major component isolated from Mitragyna speciosa Korth or kratom, a medicinal plant known for its opiate-like and euphoric properties. Multiple toxicity and fatal cases involving mitragynine or kratom have been reported but the underlying causes remain unclear. P-glycoprotein (P-gp) is a multidrug transporter which modulates the pharmacokinetics of xenobiotics and plays a key role in mediating drug-drug interactions. This study investigated the effects of mitragynine on P-gp transport activity, mRNA, and protein expression in Caco-2 cells using molecular docking, bidirectional assay, RT-qPCR, Western blot analysis, and immunocytochemistry techniques, respectively. Molecular docking simulation revealed that mitragynine interacts with important residues at the nucleotide binding domain (NBD) site of the P-gp structure but not with the residues from the substrate binding site. This was consistent with subsequent experimental work as mitragynine exhibited low permeability across the cell monolayer but inhibited digoxin transport at 10 μM, similar to quinidine. The reduction of P-gp activity in vitro was further contributed by the downregulation of mRNA and protein expression of P-gp. In summary, mitragynine is likely a P-gp inhibitor in vitro but not a substrate. Hence, concurrent administration of mitragynine-containing kratom products with psychoactive drugs which are P-gp substrates may lead to clinically significant toxicity. Further clinical study to prove this point is needed.
  8. Paudel KR, Clarence DD, Panth N, Manandhar B, De Rubis G, Devkota HP, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Apr;397(4):2465-2483.
    PMID: 37851060 DOI: 10.1007/s00210-023-02760-7
    The purpose of this study was to evaluate the potential of zerumbone-loaded liquid crystalline nanoparticles (ZER-LCNs) in the protection of broncho-epithelial cells and alveolar macrophages against oxidative stress, inflammation and senescence induced by cigarette smoke extract in vitro. The effect of the treatment of ZER-LCNs on in vitro cell models of cigarette smoke extract (CSE)-treated mouse RAW264.7 and human BCi-NS1.1 basal epithelial cell lines was evaluated for their anti-inflammatory, antioxidant and anti-senescence activities using colorimetric and fluorescence-based assays, fluorescence imaging, RT-qPCR and proteome profiler kit. The ZER-LCNs successfully reduced the expression of pro-inflammatory markers including Il-6, Il-1β and Tnf-α, as well as the production of nitric oxide in RAW 264.7 cells. Additionally, ZER-LCNs successfully inhibited oxidative stress through reduction of reactive oxygen species (ROS) levels and regulation of genes, namely GPX2 and GCLC in BCi-NS1.1 cells. Anti-senescence activity of ZER-LCNs was also observed in BCi-NS1.1 cells, with significant reductions in the expression of SIRT1, CDKN1A and CDKN2A. This study demonstrates strong in vitro anti-inflammatory, antioxidative and anti-senescence activities of ZER-LCNs paving the path for this formulation to be translated into a promising therapeutic agent for chronic respiratory inflammatory conditions including COPD and asthma.
  9. Pang CY, Mak JW, Ismail R, Ong CE
    Naunyn Schmiedebergs Arch Pharmacol, 2012 May;385(5):495-502.
    PMID: 22307090 DOI: 10.1007/s00210-012-0731-5
    The inhibitory effects of five flavonoids with distinct chemical classes (flavones [luteolin], flavonols [quercetin and quercitrin], and flavanones [hesperetin and hespiridin]) on cDNA-expressed CYP2C8 were investigated. CYP2C8 was co-expressed with NADPH-cytochrome P450 reductase in Escherichia coli and used to characterise potency and mechanism of these flavonoids on the isoform. Tolbutamide 4-methylhydroxylase, a high-performance liquid chromatography-based assay, was selected as marker activity for CYP2C8. Our results indicated that the flavonoids inhibited CYP2C8 with different potency. The order of inhibitory activities was quercetin > luteolin > hesperetin > hesperidin > quercitrin. All of these compounds however exhibited mechanism-based inhibition. A number of structural factors were found to be important for inhibition; these include the molecular shape (volume to surface ratio), the number of hydroxyl groups as well as glycosylation of the hydroxyl group. Quercetin was the most potent inhibitor among the flavonoids examined in this study, and our data suggest that it should be examined for potential pharmacokinetic drug interactions pertaining to CYP2C8 substrates in vivo.
  10. Nahar N, Mohamed S, Mustapha NM, Lau S, Ishak NIM, Umran NS
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Mar;394(3):457-467.
    PMID: 33047165 DOI: 10.1007/s00210-020-01989-w
    Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.
  11. Manandhar B, Paudel KR, Clarence DD, De Rubis G, Madheswaran T, Panneerselvam J, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Jan;397(1):343-356.
    PMID: 37439806 DOI: 10.1007/s00210-023-02603-5
    Lung cancer is the second most prevalent type of cancer and is responsible for the highest number of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) makes up the majority of lung cancer cases. Zerumbone (ZER) is natural compound commonly found in the roots of Zingiber zerumbet which has recently demonstrated anti-cancer activity in both in vitro and in vivo studies. Despite their medical benefits, ZER has low aqueous solubility, poor GI absorption and oral bioavailability that hinders its effectiveness. Liquid crystalline nanoparticles (LCNs) are novel drug delivery carrier that have tuneable characteristics to enhance and ease the delivery of bioactive compounds. This study aimed to formulate ZER-loaded LCNs and investigate their effectiveness against NSCLC in vitro using A549 lung cancer cells. ZER-LCNs, prepared in the study, inhibited the proliferation and migration of A549 cells. These inhibitory effects were superior to the effects of ZER alone at a concentration 10 times lower than that of free ZER, demonstrating a potent anti-cancer activity of ZER-LCNs. The underlying mechanisms of the anti-cancer effects by ZER-LCNs were associated with the transcriptional regulation of tumor suppressor genes P53 and PTEN, and metastasis-associated gene KRT18. The protein array data showed downregulation of several proliferation associated proteins such as AXL, HER1, PGRN, and BIRC5 and metastasis-associated proteins such as DKK1, CAPG, CTSS, CTSB, CTSD, and PLAU. This study provides evidence of potential for increasing the potency and effectiveness of ZER with LCN formulation and developing ZER-LCNs as a treatment strategy for mitigation and treatment of NSCLC.
  12. Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.
    PMID: 37266589 DOI: 10.1007/s00210-023-02553-y
    Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial-mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.
  13. Loong BJ, Tan JH, Lim KH, Mbaki Y, Ting KN
    Naunyn Schmiedebergs Arch Pharmacol, 2015 Oct;388(10):1061-7.
    PMID: 26051407 DOI: 10.1007/s00210-015-1140-3
    The functional responses of different overnight-stored in vitro tissues are not clearly described in any animal model. The influence of overnight storage in an animal model may vary between tissue types. We employed Sprague-Dawley rat as our animal model and investigated the functional changes of rat aorta, trachea, bronchus and bladder that were used (i) immediately after surgical removal (denoted as fresh) and (ii) after storage in aerated (95% O2, 5% CO2) Krebs-Ringer bicarbonate solution at 4 °C for 24 h (denoted as stored). The aorta ring was pre-contracted with phenylephrine, and the functional response of the tissue was investigated using isoprenaline, forskolin and carbachol. Carbachol was also used to increase the tone in trachea, bronchus rings and bladder strips. A clear reduced function of endothelium, with a minor if any effect in the smooth muscle function in rat aorta was observed after overnight storage. The contractile response of overnight-stored rat airway (trachea and bronchus) and bladder smooth muscles remained unchanged. Among all tested tissues, only bronchus showed a reduced response rate (only 40% responded) after storage. In vitro rat tissues that are stored in Krebs solution at 4 °C for 24 h can still be used to investigate smooth muscle responses, however, not endothelium-mediated responses for aorta. The influence of overnight storage on different tissues from an animal model (Sprague-Dawley rat in our study) also provides an insight in maximising the use of sacrificed animals.
  14. Liow KY, Chow SC
    Naunyn Schmiedebergs Arch Pharmacol, 2018 Jan;391(1):71-82.
    PMID: 29085973 DOI: 10.1007/s00210-017-1436-6
    The cathepsin B inhibitor benzyloxycarbonyl-phenylalanine-alanine-chloromethyl ketone (z-FA-CMK) was recently found to induce apoptosis at low concentrations in Jurkat T cells, while at higher concentrations, the cells die of necrosis. In the present study, we showed that z-FA-CMK readily depletes intracellular glutathione (GSH) with a concomitant increase in reactive oxygen species (ROS) generation. The toxicity of z-FA-CMK in Jurkat T cells was completely abrogated by N-acetylcysteine (NAC), suggesting that the toxicity mediated by z-FA-CMK is due to oxidative stress. We found that L-buthionine sulfoximine (BSO) which depletes intracellular GSH through the inhibition of GSH biosynthesis in Jurkat T cells did not promote ROS increase or induce cell death. However, NAC was still able to block z-FA-CMK toxicity in Jurkat T cells in the presence of BSO, indicating that the protective effect of NAC does not involve GSH biosynthesis. This is further corroborated by the protective effect of the non-metabolically active D-cysteine on z-FA-CMK toxicity. Furthermore, in BSO-treated cells, z-FA-CMK-induced ROS increased which remains unchanged, suggesting that the depletion of GSH and increase in ROS generation mediated by z-FA-CMK may be two separate events. Collectively, our results demonstrated that z-FA-CMK toxicity is mediated by oxidative stress through the increase in ROS generation.
  15. Lim JCW, Sagineedu SR, Yong ACH, Sidik SM, Wong WSF, Stanslas J
    Naunyn Schmiedebergs Arch Pharmacol, 2021 Jan;394(1):95-105.
    PMID: 32840650 DOI: 10.1007/s00210-020-01966-3
    SRS27, an andrographolide analogue, had been proven to have therapeutic properties at a dose of 3 mg/kg in both in vitro and in vivo asthma models of our previous study. The present study focuses on the pharmacokinetic and toxicity profile of this compound to provide further evidence for the development of this compound as an anti-asthma agent. A simple pharmacokinetic study was performed in female BALB/c mice to measure blood plasma concentration of the compound at therapeutic dose. At a single dose of 3 mg/kg, SRS27 had a relatively short half-life but was able to achieve a concentration range of 13-19 μM that is related to its in vitro bioactivities. With regard to toxicity profile, SRS27 appears to be safe, as no histopathological changes were observed in the liver, kidneys and ovaries of SRS27-treated female BALB/c mice. In addition, there was no significant change in the mean body weight and organ weight of the animals in the SRS27-treated groups compared with the vehicle-treated control group at the end of the treatment. This fully supports the absence of any significant changes in peripheral blood leukocyte counts of SRS27-treated mice. Rewardingly, this acute toxicity study also revealed that SRS27 has a wide therapeutic window as no toxicity symptoms were detected with a dose up to 60 mg/kg daily when tested for 14 days. These results provide strong justification for further investigation of SRS27 as a potential new anti-asthma agent.
  16. Kumari R, Negi M, Thakur P, Mahajan H, Raina K, Sharma R, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 Mar;397(3):1505-1524.
    PMID: 37755516 DOI: 10.1007/s00210-023-02694-0
    Saussurea costus (Falc.) Lipsch., commonly known as costus, is a perennial herb that has been traditionally used in various indigenous medicinal systems across Asia. Its historical prominence in traditional remedies underscores the need to explore its phytochemical composition, pharmacological properties, and potential therapeutic benefits. This review aims to provide a comprehensive overview of the available literature on the pharmacological properties, phytochemical constituents, ethnobotanical uses, and therapeutic potential of S. costus. An exhaustive search was performed across multiple electronic databases, including PubMed/MedLine, Google Scholar, Web of Science, Scopus, TRIP database, and Science Direct. Both experimental and clinical studies, as well as traditional ethnobotanical records, were considered for inclusion. The phytochemical analysis revealed that S. costus contains a plethora of bioactive compounds, including sesquiterpenes, flavonoids, and essential oils, which are responsible for its myriad of medicinal properties. The pharmacological studies have demonstrated its anti-inflammatory, anti-oxidant, anti-cancer, hepatoprotective, and immunomodulatory effects, among others. Ethnobotanical data showcased its extensive use in treating ailments like asthma, digestive disorders, and skin conditions. Some clinical trials also underscore its efficacy in certain health conditions, corroborating its traditional uses. S. costus possesses significant therapeutic potential, largely attributable to its rich phytochemical composition; the convergence of its traditional uses and modern pharmacological findings suggests promising avenues for future research, especially in drug development and understanding its mechanism of action in various ailments.
  17. Ishak NIM, Mohamed S, Madzuki IN, Mustapha NM, Esa NM
    Naunyn Schmiedebergs Arch Pharmacol, 2021 09;394(9):1907-1915.
    PMID: 34009457 DOI: 10.1007/s00210-021-02101-6
    Inflammation and compromised immune responses often increase colorectal cancer (CRC) risk. The immune-modulating effects of limonin on carcinogen/inflammation-induced colorectal cancer (CRC) were studied in mice. Male Balb/c mice were randomly assorted into three groups (n = 6): healthy control, non-treated CRC-induced (azoxymethane/dextran-sulfate-sodium AOM/DSS) control, and CRC-induced + 50 mg limonin/kg body weight. The CRC developments were monitored via macroscopic, histopathological, ELISA, and mRNA expression analyses. Limonin downregulated inflammation (TNF-α, tumor necrosis factor-α), enhanced the adaptive immune responses (CD8, CD4, and CD19), and upregulated antioxidant defense (Nrf2, SOD2) mRNA expressions. Limonin reduced serum malondialdehyde (MDA, lipid peroxidation biomarker), prostaglandin E2, and histopathology inflammation scores, while increasing reduced glutathione (GSH) in CRC-induced mice. Limonin significantly (p 
  18. Gulati N, Chellappan DK, MacLoughlin R, Gupta G, Singh SK, Oliver BG, et al.
    PMID: 38078921 DOI: 10.1007/s00210-023-02882-y
    Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.
  19. Garg P, Pundir S, Ali A, Panja S, Chellappan DK, Dua K, et al.
    PMID: 38055069 DOI: 10.1007/s00210-023-02862-2
    Moringa oleifera Lam. is a pan-tropical plant well known to the ancient world for its extensive therapeutic benefits in the Ayurvedic and Unani medical systems. The ancient world was familiar with this tree, but it has only lately been rediscovered as a multifunctional species with a huge range of possible therapeutic applications. It is a folk remedy for skin diseases, edema, sore gums, etc. This review comprises the history, ethnomedicinal applications, botanical characteristics, geographic distribution, propagation, nutritional and phytochemical profile, dermatological effects, and commercially available cosmeceuticals of Moringa oleifera Lam.Compilation of all the presented data has been done by employing various search engines like Science Direct, Google, PubMed, Research Gate, EBSCO, SciVal, SCOPUS, and Google Scholar.Studies on phytochemistry claim the presence of a variety of substances, including fatty acids, phenolic acids, sterols, oxalates, tocopherols, carotenoids, flavonoids, flavonols glycosides, tannins, terpenoids, terpene, saponins, phylates, alkaloids, glucosinolates, glycosides, and isothiocyanate. The pharmacological studies have shown the efficacy of Moringa oleifera Lam. as an antibacterial, antifungal, anti-inflammatory, antioxidant, anti-atopic dermatitis, antipsoriatic, promoter of wound healing, effective in treating herpes simplex virus, photoprotective, and UV protective. As a moisturizer, conditioner, hair growth promoter, cleanser, antiwrinkle, anti-aging, anti-acne, scar removal, pigmentation, and control for skin infection, sores, as well as sweating, it has also been utilized in a range of cosmeceuticals.he Moringa oleifera Lam. due to its broad range of phytochemicals can be proven boon for the treatment of dermatological disorders.
  20. Dong AN, Ahemad N, Pan Y, Palanisamy UD, Yiap BC, Ong CE
    Naunyn Schmiedebergs Arch Pharmacol, 2019 08;392(8):1015-1029.
    PMID: 31025144 DOI: 10.1007/s00210-019-01651-0
    One major source of inter-individual variability in drug pharmacokinetics is genetic polymorphism of the cytochrome P450 (CYP) genes. This study aimed to elucidate the enzyme kinetic and molecular basis for altered activity in three major alleles of CYP2D6, namely CYP2D6*2, CYP2D6*10 and CYP2D6*17. The E. coli-expressed allelic variants were examined using substrate (venlafaxine and 3-cyano-7-ethoxycoumarin[CEC]) and inhibitor (quinidine, fluoxetine, paroxetine, terbinafine) probes in enzyme assays as well as molecular docking. The kinetics data indicated that R296C and S486T mutations in CYP2D6*2 have caused enhanced ligand binding (enhanced intrinsic clearance for venlafaxine and reduced IC50 for quinidine, paroxetine and terbinafine), suggesting morphological changes within the active site cavity that favoured ligand docking and binding. Mutations in CYP2D6*10 and CYP2D6*17 tended to cause deleterious effect on catalysis, with reduced clearance for venlafaxine and CEC. Molecular docking indicated that P34S and T107I, the unique mutations in the alleles, have negatively impacted activity by affecting ligand access and binding due to alteration of the substrate access channel and active site morphology. IC50 values however were quite variable for quinidine, fluoxetine and terbinafine, and a general decrease in IC50 was observed for paroxetine, suggesting ligand-specific altered susceptibility to inhibition in the alleles. This study indicates that CYP2D6 allele selectivity for ligands was not solely governed by changes in the active site architecture induced by the mutations, but that the intrinsic properties of the substrates and inhibitors also played vital role.
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