Preclinical pharmacokinetic studies of villocarine A, an active Uncaria alkaloid.

Villocarine A is a bioactive indole alkaloid isolated from the Uncaria genus. It has demonstrated vasorelaxation activity and potential to protect the central nervous system. To identify the pharmacokinetic properties of villocarine A, a series of in vitro and in vivo studies have been performed. Villocarine A was found to be highly permeable (15.6 ± 1.6*10-6 cm/s) across human colorectal adenocarcinoma cell monolayer with high protein binding (>91%) in both rat and human plasma. Hepatic extraction ratio of villocarine A was 0.1 in pooled rat liver and 0.2 in human liver microsomes and was found stable in rat plasma at 37°C. Due to the high permeability and low rate of metabolism properties, villocarine A was initially considered suitable for preclinical development and an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for quantification (linearity: 1-150 ng/ml) in rat plasma was developed and validated for in vivo studies. Essential pharmacokinetic parameters included the volume of distribution and clearance of villocarine A, which were found to be 100.3 ± 15.6 L/kg and 8.2 ± 1.1 L/h/kg, respectively, after intravenous administration in rats. Following oral dosing, villocarine A exhibited rapid absorption as the maximum plasma concentration (53.2 ± 10.4 ng/ml) occurred at 0.3 ± 0.1 h, post-dose. The absolute oral bioavailability of villocarine A was 16.8 ± 0.1%. To our knowledge, this was the first pharmacokinetic study of villocarine A, which demonstrated the essential pharmacokinetic properties of villocarine A: large volume distribution, high clearance, and low oral bioavailability in rats.

Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a common mechanism of acute brain injury due to impairment of blood flow to the brain. Moreover, a prolonged lack of oxygen supply may result in cerebral infarction or global ischemia, which subsequently causes long-term memory impairment. Research on using Clitoria ternatea root extract for treating long-term memory has been studied extensively. However, the bioactive compound contributing to its neuroprotective effects remains uncertain. In the present study, we investigate the effects of clitorienolactone A (CLA) and B (CLB) from the roots of Clitoria ternatea extract on hippocampal neuroplasticity in rats induced by CCH. CLA and CLB were obtained using column chromatography. The rat model of CCH was induced using two-vessel occlusion surgery (2VO). The 2VO rats were given 10 mg/kg of CLA and CLB orally, followed by hippocampal neuroplasticity recording using in vivo electrophysiological. Rats received CLA and CLB (10 mg/kg) significantly reversed the impairment of long-term potentiation following 2VO surgery. Furthermore, we investigate the effect of CLA and CLB on the calcium channel using the calcium imaging technique. During hypoxia, CLA and CLB sustain the increase in intracellular calcium levels. We next predict the binding interactions of CLA and CLB against NMDA receptors containing GluN2A and GluN2B subunits using in silico molecular docking. Our result found that both CLA and CLB exhibited lower binding affinity against GluN2A and GluN2B subunits. Our findings demonstrated that bioactive compounds from Clitoria ternatea improved long-term memory deficits in the chronic cerebral hypoperfusion rat model via calcium uptake. Hence, CLA and CLB could be potential therapeutic tools for treating cognitive dysfunction.

Chitosan-Based Nanoencapsulated Essential Oils: Potential Leads against Breast Cancer Cells in Preclinical Studies.

Since ancient times, essential oils (EOs) derived from aromatic plants have played a significant role in promoting human health. EOs are widely used in biomedical applications due to their medicinal properties. EOs and their constituents have been extensively studied for treating various health-related disorders, including cancer. Nonetheless, their biomedical applications are limited due to several drawbacks. Recent advances in nanotechnology offer the potential for utilising EO-loaded nanoparticles in the treatment of various diseases. In this aspect, chitosan (CS) appears as an exceptional encapsulating agent owing to its beneficial attributes. This review highlights the use of bioactive EOs and their constituents against breast cancer cells. Challenges associated with the use of EOs in biomedical applications are addressed. Essential information on the benefits of CS as an encapsulant, the advantages of nanoencapsulated EOs, and the cytotoxic actions of CS-based nanoencapsulated EOs against breast cancer cells is emphasised. Overall, the nanodelivery of bioactive EOs employing polymeric CS represents a promising avenue against breast cancer cells in preclinical studies.

Evaluation of toxicity profile of kratom (Mitragyna speciosa Korth) decoction in rats.

Mitragyna speciosa Korth also known as kratom, is an herbal drug preparation for its therapeutic properties and opioid-replacement therapy. Kratom is consumed in a brewed decoction form in Malaysia and to date, no studies have characterized its chemical and toxicity profile. Thus, this study aims to evaluate kratom decoction's safety and toxicity profile after 28 days of treatment. Mitragynine content was quantified in kratom decoction and used as a marker to determine the concentration. Male and female Sprague Dawley rats were orally treated with vehicle or kratom decoction (10, 50 or 150 mg/kg) and two satellite groups were treated with vehicle and kratom decoction (150 mg/kg). Blood and organs were collected for hematology, biochemical and histopathology analysis at the end of treatment. No mortality was found after 28 days of treatment and no significant changes in body weight and hematology profile, except for low platelet count. High amounts of uric acid, AST, ALT and alkaline phosphatase were found in the biochemical analysis. Histological investigation of the heart and lungs detected no alterations except for the kidney, liver and brain tissues. In conclusion, repeated administration of kratom decoction provided some evidence of toxicity in the kidney and liver with no occurrence of mortality.

Bio-enhanced fraction from Clitoria ternatea root extract ameliorates cognitive functions and in vivo hippocampal neuroplasticity in chronic cerebral hypoperfusion rat model.

Research employing a bio-enhanced fraction of Clitoria ternatea (CT) to treat cognitive decline in the animal model has not yet been found. This study aimed to determine the neuroprotective effect of CT root bioactive fraction (CTRF) in chronic cerebral hypoperfusion (CCH) rat model. CTRF and its major compound, clitorienolactones A (CLA), were obtained using column chromatography. A validated HPLC-UV method was employed for the standardization of CTRF. CCH rats were given orally either vehicle or fraction (10, 20 and 40 mg/kg). Behavioural and hippocampal neuroplasticity studies were conducted following 4 weeks post-surgery. The brain hippocampus was extracted for proteins and neurotransmitters analyses. HPLC analysis showed that CTRF contained 25% (w/w) of CLA. All tested doses of CTRF and CLA (10 mg/kg) significantly restored cognitive deficits and reversed the inhibition of neuroplasticity by CCH. However, only CTRF (40 mg/kg) and CLA (10 mg/kg) significantly reversed the elevation of amyloid-beta plaque. Subsequently, treatment with CTRF (40 mg/kg) and CLA (10 mg/kg) alleviated the downregulation of molecular synaptic signalling proteins levels caused by CCH. The neurotransmitters level was restored following treatment of CTRF and CLA. Our finding suggested that CTRF improves memory and neuroplasticity in CCH rats which was mainly contributed by CLA.

Natural Corynanthe-Type Cholinesterase Inhibitors from Malaysian Uncaria attenuata Korth.: Isolation, Characterization, In Vitro and In Silico Studies.

The Uncaria genus is notable for its therapeutic potential in treating age-related dementia, such as Alzheimer's disease. A phytochemical study of the leaves of Malaysian Uncaria attenuata Korth., afforded an undescribed natural corynanthe-type oxindole alkaloid, isovillocarine D (1) together with two known indole alkaloids, villocarine A (2) and geissoschizine methyl ether (3), and their structural identification was performed with extensive mono- and bidimensional NMR and MS spectroscopic methods. The isolated alkaloids were evaluated for their acetylcholinesterase (AChE)- and butyrylcholinesterase (BChE)-inhibitory activity. The results indicated that compound (2) was the most potent inhibitor against both AChE and BChE, with IC50 values of 14.45 and 13.95 µM, respectively, whereas compounds (1) and (3) were selective BChE inhibitors with IC50 values of 35.28 and 17.65 µM, respectively. In addition, molecular docking studies revealed that compound (2) interacts with the five main regions of AChE via both hydrogen and hydrophobic bonding. In contrast to AChE, the interactions of (2) with the enzymatic site of BChE are established only through hydrophobic bonding. The current finding suggests that U. attenuata could be a good source of bioactive alkaloids for treating age-related dementia.

Metabolites characterisation of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera with antimicrobial activity on diabetic wound microorganisms.

This study aimed to assess the antimicrobial activity of endophytic Phyllosticta fallopiae L67 isolated from Aloe vera against diabetic wound microorganisms and characterise their active fraction for biologically important metabolites. The dichloromethane (DCM) extract exhibited the most significant activity with inhibition zones ranging from 11.33 to 38.33 mm. The minimal inhibitory and lethality concentrations of DCM extract ranged from 78.13 to 2500.00 µg/ml and 625.00 to 5000.00 µg/ml, respectively. The extract showed teratogenicity and lethality in the zebrafish model, where peritoneal and hepatic oedema occurred at 62.50 µg/ml, and no abnormality appeared at 31.25 µg/ml. The extract also inhibited more than 82% biofilm formation. Bioassay-guided fractionation on DCM extract yielded 18 fractions and the most active fraction was subjected to UPLC-QTOF-MS/MS analysis. Flavones, stilbenes, flavanonols, isoflavonoids, phenolic glycosides and phenol derivatives were detected. In conclusion, endophytic P. fallopiae possessed bioactive metabolites with significant antimicrobial activity against diabetic wound microorganisms.

Adolescent kratom exposure affects cognitive behaviours and brain metabolite profiles in Sprague-Dawley rats.

Adolescence is a critical developmental period during which exposure to psychoactive substances like kratom (Mitragyna speciosa) can cause long-lasting deleterious effects. Here, we evaluated the effects of mitragynine, the main alkaloid of kratom, and lyophilised kratom decoction (LKD) on cognitive behaviours and brain metabolite profiles in adolescent rats. Male Sprague-Dawley rats (Postnatal day, PND31) were given vehicle, morphine (5 mg/kg), mitragynine (3, 10, or 30 mg/kg), or LKD (equivalent dose of 30 mg/kg mitragynine) for 15 consecutive days. Later, a battery of behavioural testing was conducted, brain was extracted and metabolomic analysis was performed using LCMS-QTOF. The results showed that mitragynine did not affect the recognition memory in the novel object recognition task. In the social interaction task, morphine, mitragynine, and LKD caused a marked deficit in social behaviour, while in Morris water maze task, mitragynine and LKD only affected reference memory. Metabolomic analysis revealed distinct metabolite profiles of animals with different treatments. Several pathways that may be involved in the effects of kratom exposure include arachidonic acid, pantothenate and CoA, and tryptophan pathways, with several potential biomarkers identified. These findings suggest that adolescent kratom exposure can cause cognitive behavioural deficits that may be associated with changes in the brain metabolite profiles.

Metabolomics Analysis and Antioxidant Potential of Endophytic Diaporthe fraxini ED2 Grown in Different Culture Media.

Endophytic fungi are a promising source of bioactive metabolites with a wide range of pharmacological activities. In the present study, MS-based metabolomics was conducted to study the metabolomes variations of endophytic Diaporthe fraxini ED2 grown in different culture media. Total phenolic content (TPC), total flavonoid content (TFC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays were conducted to assess the antioxidant potential of the fungal extracts. Multivariate data analysis (MVDA) was employed in data analysis and interpretation to elucidate the complex metabolite profile. The supplemented culture medium of D. fraxini fungal extract stimulated the production of metabolites not occurring in the normal culture medium. Antioxidant activity studies revealed the potential of supplemented cultured fungal extract of D. fraxini as a source of antioxidants. The present findings highlight that fungal culture medium supplementation is an effective approach to unravelling the hidden metabolome in plant-associated fungal diversity.

Safe and selective anticancer agents from tetrafluorinated azobenzene-imidazolium ionic liquids: Synthesis, characterization, and cytotoxic effects.

A new series of tetrafluorinated azobenzene-imidazolium salts is reported. The azobenzene and imidazolium moieties were functionalized with long alkyl chains and connected via a methylene spacer of varying lengths (n = 3-12). They were characterized using FTIR and NMR spectroscopy, and elemental microanalysis. The cytotoxic potential of these ionic dimers against neuroblastoma (SHSY-5Y), estrogen-positive breast cancer cells (MCF-7), triple-negative breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa), and human skin fibroblasts (Hs27) was evaluated using the MTT assay. The cytotoxicity of these ionic liquids (ILs) was dependent on the spacer length. A cut-off effect was observed, wherein the cytotoxicity of the ILs was enhanced by increasing the nonpolar, hydrophobic spacer length up to a threshold and the potency was leveled off upon chain elongation. All ILs exhibited selective and remarkable inhibition potentials against HeLa cells in a dose-dependent manner, which was 2-22 times stronger than that of etoposide, a clinical anticancer drug. These ILs were less toxic toward skin fibroblasts as implied by much higher IC50 values. The long-spacer ILs (n = 7-10) were very selective toward HeLa cells. They had a broad safety window with selectivity indices ranging between 5.6 and 11.0. The selectivity of these compounds toward HeLa cells may serve as a new strategy for the design and development of safe and effective chemotherapeutics.

Plant Terpenoids as the Promising Source of Cholinesterase Inhibitors for Anti-AD Therapy.

Plant-derived terpenes are the prolific source of modern drugs such as taxol, chloroquine and artemisinin, which are widely used to treat cancer and malaria infections. There are research interests in recent years on terpene-derived metabolites (diterpenes, triterpenes and sesquiterpenes), which are believed to serve as excellent cholinesterase inhibitors. As cholinesterase inhibitors are the current treatment for Alzheimer's disease, terpene-derived metabolites will have the potential to be involved in the future drug development for Alzheimer's disease. Hence, a bibliographic search was conducted by using the keywords "terpene", "cholinesterase" and "Alzheimer's disease", along with cross-referencing from 2011 to 2020, to provide an overview of natural terpenes with potential anticholinesterase properties. This review focuses on the extraction, chemical structures and anti-cholinesterase mechanisms of terpenes, which support and encourage future research on drug discovery and development in treating Alzheimer's disease.

Kratom Alkaloids: Interactions With Enzymes, Receptors, and Cellular Barriers.

Parallel to the growing use of kratom, there is a wealth of evidence from self-report, preclinical, and early clinical studies on therapeutic benefits of its alkaloids in particular for treating pain, managing substance use disorder, and coping with emotional or mental health conditions. On the other hand, there are also reports on potential health risks concerning kratom use. These two aspects are often discussed in reviews on kratom. Here, we aim to highlight specific areas that are of importance to give insights into the mechanistic of kratom alkaloids pharmacological actions. This includes their interactions with drug-metabolizing enzymes and predictions of clinical drug-drug interactions, receptor-binding properties, interactions with cellular barriers in regards to barrier permeability, involvement of membrane transporters, and alteration of barrier function when exposed to the alkaloids.

Comparative Toxicity Assessment of Kratom Decoction, Mitragynine and Speciociliatine Versus Morphine on Zebrafish (Danio rerio) Embryos.

Background: Kratom (Mitragyna speciosa Korth), a popular opioid-like plant holds its therapeutic potential in pain management and opioid dependence. However, there are growing concerns about the safety or potential toxicity risk of kratom after prolonged use. Aim of the study: The study aimed to assess the possible toxic effects of kratom decoction and its major alkaloids, mitragynine, and speciociliatine in comparison to morphine in an embryonic zebrafish model. Methods: The zebrafish embryos were exposed to kratom decoction (1,000-62.5 µg/ml), mitragynine, speciociliatine, and morphine (100-3.125 µg/ml) for 96 h post-fertilization (hpf). The toxicity parameters, namely mortality, hatching rate, heart rate, and morphological malformations were examined at 24, 48, 72, and 96 hpf, respectively. Results: Kratom decoction at a concentration range of ≥500 µg/ml caused 100% mortality of zebrafish embryos and decreased the hatching rate in a concentration-dependent manner. Meanwhile, mitragynine and speciociliatine exposure resulted in 100% mortality of zebrafish embryos at 100 µg/ml. Both alkaloids caused significant alterations in the morphological development of zebrafish embryos including hatching inhibition and spinal curvature (scoliosis) at the highest concentration. While exposure to morphine induced significant morphological malformations such as pericardial oedema, spinal curvature (lordosis), and yolk edema in zebrafish embryos. Conclusion: Our findings provide evidence for embryonic developmental toxicity of kratom decoction and its alkaloids both mitragynine and speciociliatine at the highest concentration, hence suggesting that kratom consumption may have potential teratogenicity risk during pregnancy and thereby warrants further investigations.

Rapid spheroid assays in a 3-dimensional cell culture chip.

OBJECTIVE: The spheroid model provides a physiological platform to study cancer cell biology and drug sensitivity. Usage of bovine collagen I for spheroid assays is costly especially when experiments are conducted in 24-well plates, as high volume of bovine collagen I is needed. The aim of the study was to downsize spheroid assays to a microfluidic 3D cell culture chip and compare the growth, invasion and response to drug/compound of spheroids embedded in the 3D chip to spheroids embedded in 24-well plates. RESULTS: Spheroids generated from nasopharyngeal carcinoma cell line HK-1 continuously grew and invaded into collagen matrix in a 24-well plate. Similar observations were noticed with spheroids embedded in the 3D chip. Large spheroids in both 24-well plate and the 3D chip disintegrated and invaded into the collagen matrix. Preliminary drug sensitivity assays showed that the growth and invasion of spheroids were inhibited when spheroids were treated with combination of cisplatin and paynantheine at high concentrations, in a 24-well plate. Comparable findings were obtained when spheroids were treated with the same drug combination in the 3D chip. Moving forward, spheroid assays could be performed in the 3D chip in a more high-throughput manner with minimal time and cost.

The potentiation of beta-lactam and anti-bacterial activities of lipophilic constituents from Mesua ferrae leaves against methicillin-resistant Staphylococcus aureus.

OBJECTIVES: Mesua ferrae, from the family of Calophyllaceae, is traditionally used for the treatment of piles, fever and renal disorders. The present study was aimed to examine the antibacterial compounds from the leaves of M. ferrae and their ß-lactam antibiotic potentiate activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Stigmasterol (1) and ß-caryophyllene oxide (2) were isolated from the n-hexane fraction of the leaves of M. ferrae using a bioassay-guided fractionation approach. RESULTS: The isolated compounds displayed anti-Staphylococcus and anti-MRSA activities. It is worth to note that both compounds demonstrated synergism with ß-lactam antibiotics against S. aureus and MRSA. Gas chromatography-mass spectrometry (GC-MS) analysis indicated the n-hexane fraction was dominated by triterpenes and sesquiterpenes, suggesting the total antibacterial activity exhibited by the fraction. CONCLUSION: Based on the findings, it could conclude that M. ferrae is a promising natural source for the discovery of new anti-MRSA lead compounds.

Chemical Composition, Antioxidant and Cytoprotective Potentials of Carica papaya Leaf Extracts: A Comparison of Supercritical Fluid and Conventional Extraction Methods.

The leaves of Carica papaya (CP) are rich in natural antioxidants. Carica papaya has traditionally been used to treat various ailments, including skin diseases. This study aims to decipher the antioxidant effects and phytochemical content of different CP leaf extracts (CPEs) obtained using supercritical carbon dioxide (scCO2) and conventional extraction methods. The antioxidant activities of CPEs were evaluated by cell-free (1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric-reduced antioxidative power (FRAP)) and cell-based (H2O2) assay. Both C. papaya leaf scCO2 extract with 5% ethanol (CPSCE) and C. papaya leaf scCO2 extract (CPSC) exhibited stronger DPPH radical scavenging activity than conventional extracts. In the FRAP assay, two hydrophilic extracts (C. papaya leaf ethanol extract (CPEE) and C. papaya freeze-dried leaf juice (CPFD)) showed relatively stronger reducing power compared to lipophilic extracts. Cell-based assays showed that CPFD significantly protected skin fibroblasts from H2O2-induced oxidative stress in both pre-and post-treatment. CPEE protected skin fibroblasts from oxidative stress in a dose-dependent manner while CPSCE significantly triggered the fibroblast recovery after treatment with H2O2. GC-MS analysis indicated that CPSCE had the highest α-tocopherol and squalene contents. By contrast, both CP hydrophilic extracts (CPEE and CPFD) had a higher total phenolic content (TPC) and rutin content than the lipophilic extracts. Overall, CPEs extracted using green and conventional extraction methods showed antioxidative potential in both cell-based and cell-free assays due to their lipophilic and hydrophilic antioxidants, respectively.

Exploring the Chemistry of Alkaloids from Malaysian Mitragyna speciosa (Kratom) and the Role of Oxindoles on Human Opioid Receptors.

Ten indole and oxindole alkaloids (1-10) were isolated from the freshly collected leaves of Malaysian Mitragyna speciosa (Kratom). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data analysis. The spectroscopic data of mitragynine oxindole B (4) are reported herein for the first time. The spatial configuration of mitragynine oxindole B (4) was confirmed by single-crystal X-ray diffraction. Simultaneous quantification of the isolated alkaloids in the M. speciosa leaf specimens collected from different locations in the northern region of Peninsular Malaysia was also performed using UPLC-MS/MS. The oxindole alkaloids (1-4) and the indole alkaloid (10) were assessed for binding affinity at opioid receptors. Corynoxine (1) showed high binding affinity to µ-opioid receptors with a Ki value of 16.4 nM. Further, corynoxine (1) was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay. These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity of M. speciosa.

Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls.

OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects. METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method. RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg. CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

Chemical composition, antiproliferative and antioxidant attributes of ethanolic extract of resinous sediment from Etlingera elatior (Jack. ) inflorescence

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 µg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 µg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro

Lipid profile of regular kratom (Mitragyna speciosa Korth.) users in the community setting.

BACKGROUND AND AIM: Kratom, or Mitragyna speciosa Korth., is a tropical plant that has been reported to exhibit opioid-like effects. Although opioids have been demonstrated to alter the lipid profile of regular users, data on the lipid-altering effects of kratom are scarce. This study aimed to compare the fasting lipid profile of regular kratom users to that of healthy subjects who do not use kratom. It also determined the association between various characteristics of kratom users and the serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels of regular kratom users. METHODS: A total of 200 participants (n = 100 kratom users and n = 100 healthy subjects who do not use kratom) were recruited for this analytical cross-sectional study. Data on sociodemographic status, kratom use characteristics, cigarette smoking, physical activity, body mass index (BMI), fasting serum lipid profile, and liver function were collected from all participants. RESULTS: The liver parameters of the study participants were within normal range. The serum total cholesterol and LDL of kratom users were significantly lower than those of healthy subjects who do not use kratom. There were no significant differences in the serum triglyceride and HDL levels. However, higher average daily frequency of kratom use and increasing age were associated with increased serum total cholesterol among kratom users. Other kratom use characteristics such as age of first kratom intake, duration of kratom use, and quantity of daily kratom intake were not associated with increased serum triglyceride, total cholesterol, LDL, and HDL levels. CONCLUSIONS: Our findings suggest regular kratom consumption was not linked to elevated serum lipids, except when there is a higher frequency of daily kratom intake. However, the study was limited by the small sample size, and hence a more comprehensive study with larger sample size is warranted to confirm the findings.