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Trigonelline attenuates the adipocyte differentiation and lipid accumulation in 3T3-L1 cells

Ilavenil S, Arasu MV, Lee JC, Kim DH, Roh SG, Park HS, et al.

Phytomedicine, 2014 Apr 15;21(5):758-65.
PMID: 24369814 DOI: 10.1016/j.phymed.2013.11.007

Trigonelline is a natural alkaloid mainly found in Trigonella Foenum Graecum (fenugreek) Fabaceae and other edible plants with a variety of medicinal applications. Therefore, we investigated the molecular mechanism of trigonelline (TG) on the inhibition of adipocyte differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline suppressed lipid droplet accumulation in a concentration (75 and 100 μM) dependent manner. Treatment of adipocyte with of TG down regulates the peroxisome proliferator-activated receptor (PPARγ) and CCAAT element binding protein (C/EBP-α) mRNA expression, which leads to further down regulation of other gene such as adiponectin, adipogenin, leptin, resistin and adipocyte fatty acid binding protein (aP2) as compared with respective control cells on 5th and 10th day of differentiation. Further, addition of triognelline along with troglitazone to the adipocyte attenuated the troglitazone effects on PPARγ mediated differentiation and lipid accumulation in 3T3-L1 cells. Trigonelline might compete against troglitazone for its binding to the PPARγ. In addition, adipocyte treated with trigonelline and isoproterenol separately. Isoproterenol, a lipolytic agent which inhibits the fatty acid synthase and GLUT-4 transporter expression via cAMP mediated pathway, we found that similar magnitude response of fatty acid synthase and GLUT-4 transporter expression in trigonelline treated adipocyte. These results suggest that the trigonelline inhibits the adipogenesis by its influences on the expression PPARγ, which leads to subsequent down regulation of PPAR-γ mediated pathway during adipogenesis. Our findings provide key approach to the mechanism underlying the anti-adipogenic activity of trigonelline.

Matched MeSH terms: Alkaloids/pharmacology
Fulltext The natural alkaloid Jerantinine B has activity in acute myeloid leukemia cells through a mechanism involving c-Jun

Alhuthali HM, Bradshaw TD, Lim KH, Kam TS, Seedhouse CH

BMC Cancer, 2020 Jul 07;20(1):629.
PMID: 32635894 DOI: 10.1186/s12885-020-07119-2

BACKGROUND: Acute myeloid leukemia (AML) is a heterogenous hematological malignancy with poor long-term survival. New drugs which improve the outcome of AML patients are urgently required. In this work, the activity and mechanism of action of the cytotoxic indole alkaloid Jerantinine B (JB), was examined in AML cells.
METHODS: We used a combination of proliferation and apoptosis assays to assess the effect of JB on AML cell lines and patient samples, with BH3 profiling being performed to identify early effects of the drug (4 h). Phosphokinase arrays were adopted to identify potential driver proteins in the cellular response to JB, the results of which were confirmed and extended using western blotting and inhibitor assays and measuring levels of reactive oxygen species.
RESULTS: AML cell growth was significantly impaired following JB exposure in a dose-dependent manner; potent colony inhibition of primary patient cells was also observed. An apoptotic mode of death was demonstrated using Annexin V and upregulation of apoptotic biomarkers (active caspase 3 and cleaved PARP). Using BH3 profiling, JB was shown to prime cells to apoptosis at an early time point (4 h) and phospho-kinase arrays demonstrated this to be associated with a strong upregulation and activation of both total and phosphorylated c-Jun (S63). The mechanism of c-Jun activation was probed and significant induction of reactive oxygen species (ROS) was demonstrated which resulted in an increase in the DNA damage response marker γH2AX. This was further verified by the loss of JB-induced C-Jun activation and maintenance of cell viability when using the ROS scavenger N-acetyl-L-cysteine (NAC).
CONCLUSIONS: This work provides the first evidence of cytotoxicity of JB against AML cells and identifies ROS-induced c-Jun activation as the major mechanism of action.

Matched MeSH terms: Indole Alkaloids/pharmacology*
The inhibitory effects of mitragynine on P-glycoprotein in vitro

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.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Fulltext The growth suppressing effects of girinimbine on HepG2 involve induction of apoptosis and cell cycle arrest

Syam S, Abdul AB, Sukari MA, Mohan S, Abdelwahab SI, Wah TS

Molecules, 2011 Aug 23;16(8):7155-70.
PMID: 21862957 DOI: 10.3390/molecules16087155

Murraya koenigii is an edible herb widely used in folk medicine. Here we report that girinimbine, a carbazole alkaloid isolated from this plant, inhibited the growth and induced apoptosis in human hepatocellular carcinoma, HepG2 cells. The MTT and LDH assay results showed that girinimbine decreased cell viability and increased cytotoxicity in a dose-and time-dependent manner selectively. Girinimbine-treated HepG2 cells showed typical morphological features of apoptosis, as observed from normal inverted microscopy and Hoechst 33342 assay. Furthermore, girinimbine treatment resulted in DNA fragmentation and elevated levels of caspase-3 in HepG2 cells. Girinimbine treatment also displayed a time-dependent accumulation of the Sub-G(0)/G(1) peak (hypodiploid) and caused G(0)/G(1)-phase arrest. Together, these results demonstrated for the first time that girinimbine could effectively induce programmed cell death in HepG2 cells and suggests the importance of conducting further investigations in preclinical human hepatocellular carcinoma models, especially on in vivo efficacy, to promote girinimbine for use as an anticancer agent against hepatocellular carcinoma.

Matched MeSH terms: Alkaloids/pharmacology*
The Significance of Tinospora crispa in Treatment of Diabetes Mellitus

Thomas A, Rajesh EK, Kumar DS

Phytother Res, 2016 Mar;30(3):357-66.
PMID: 26749336 DOI: 10.1002/ptr.5559

Tinospora crispa is a medicinal plant belonging to the botanical family Menispermiaceae. The plant is widely distributed in Southeast Asia and the northeastern region of India. A related species Tinospora cordifolia is used in Ayurveda for treating a large spectrum of diseases. Traditional healers of Thailand, Malaysia, Guyana, Bangladesh and the southern Indian province of Kerala use this plant in the treatment of diabetes. Many diterpenes, triterpenes, phytosteroids, alkaloids and their glycosides have been isolated from T. crispa. Cell culture and animal studies suggest that the herb stimulates secretion of insulin from β-cells. It also causes dose-dependent and time-dependent enhancement of glucose uptake in muscles. However, in view of the reported hepatotoxicity, this herb may be used with caution. This article reviews the animal studies and human clinical trials carried out using this herb. Areas of future research are also identified.

Matched MeSH terms: Alkaloids/pharmacology
Fulltext Sustainable Syntheses of (-)-Jerantinines A & E and Structural Characterisation of the Jerantinine-Tubulin Complex at the Colchicine Binding Site

Smedley CJ, Stanley PA, Qazzaz ME, Prota AE, Olieric N, Collins H, et al.

Sci Rep, 2018 Jul 13;8(1):10617.
PMID: 30006510 DOI: 10.1038/s41598-018-28880-2

The jerantinine family of Aspidosperma indole alkaloids from Tabernaemontana corymbosa are potent microtubule-targeting agents with broad spectrum anticancer activity. The natural supply of these precious metabolites has been significantly disrupted due to the inclusion of T. corymbosa on the endangered list of threatened species by the International Union for Conservation of Nature. This report describes the asymmetric syntheses of (-)-jerantinines A and E from sustainably sourced (-)-tabersonine, using a straight-forward and robust biomimetic approach. Biological investigations of synthetic (-)-jerantinine A, along with molecular modelling and X-ray crystallography studies of the tubulin-(-)-jerantinine B acetate complex, advocate an anticancer mode of action of the jerantinines operating via microtubule disruption resulting from binding at the colchicine site. This work lays the foundation for accessing useful quantities of enantiomerically pure jerantinine alkaloids for future development.

Matched MeSH terms: Indole Alkaloids/pharmacology*
Fulltext Subditine, a new monoterpenoid indole alkaloid from bark of Nauclea subdita (Korth.) Steud. induces apoptosis in human prostate cancer cells

Liew SY, Looi CY, Paydar M, Cheah FK, Leong KH, Wong WF, et al.

PLoS One, 2014;9(2):e87286.
PMID: 24551054 DOI: 10.1371/journal.pone.0087286

In this study, a new apoptotic monoterpenoid indole alkaloid, subditine (1), and four known compounds were isolated from the bark of Nauclea subdita. Complete (1)H- and (13)C- NMR data of the new compound were reported. The structures of isolated compounds were elucidated with various spectroscopic methods such as 1D- and 2D- NMR, IR, UV and LCMS. All five compounds were screened for cytotoxic activities on LNCaP and PC-3 human prostate cancer cell-lines. Among the five compounds, the new alkaloid, subditine (1), demonstrated the most potent cell growth inhibition activity and selective against LNCaP with an IC50 of 12.24±0.19 µM and PC-3 with an IC50 of 13.97±0.32 µM, compared to RWPE human normal epithelial cell line (IC50 = 30.48±0.08 µM). Subditine (1) treatment induced apoptosis in LNCaP and PC-3 as evidenced by increased cell permeability, disruption of cytoskeletal structures and increased nuclear fragmentation. In addition, subditine (1) enhanced intracellular reactive oxygen species (ROS) production, as reflected by increased expression of glutathione reductase (GR) to scavenge damaging free radicals in both prostate cancer cell-lines. Excessive ROS could lead to disruption of mitochondrial membrane potential (MMP), release of cytochrome c and subsequent caspase 9, 3/7 activation. Further Western blot analyses showed subditine (1) induced down-regulation of Bcl-2 and Bcl-xl expression, whereas p53 was up-regulated in LNCaP (p53-wild-type), but not in PC-3 (p53-null). Overall, our data demonstrated that the new compound subditine (1) exerts anti-proliferative effect on LNCaP and PC-3 human prostate cancer cells through induction of apoptosis.

Matched MeSH terms: Alkaloids/pharmacology*; Indole Alkaloids/pharmacology*
Strychnan and secoangustilobine A type alkaloids from Alstonia spatulata. Revision of the C-20 configuration of scholaricine

Tan SJ, Low YY, Choo YM, Abdullah Z, Etoh T, Hayashi M, et al.

J Nat Prod, 2010 Nov 29;73(11):1891-7.
PMID: 21043460 DOI: 10.1021/np100552b

A total of 25 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia spatulata, of which five are new alkaloids of the strychnan type (alstolucines A-E, 1-5) and the other, a new alkaloid of the secoangustilobine A type (alstolobine A, 6). The structures of these alkaloids were established using NMR and MS analysis and, in the case of alstolucine B (2), also confirmed by X-ray diffraction analysis. A reinvestigation of the stereochemical assignment of scholaricine (13) by NMR and X-ray analyses indicated that the configuration at C-20 required revision. Alkaloids 1, 2, 6, 7, 9, 10, and 13 reversed multidrug resistance in vincristine-resistant KB cells.

Matched MeSH terms: Indole Alkaloids/pharmacology
Social Functioning of Kratom (Mitragyna speciosa) Users in Malaysia

Singh D, Müller CP, Vicknasingam BK, Mansor SM

J Psychoactive Drugs, 2015 5 8;47(2):125-31.
PMID: 25950592 DOI: 10.1080/02791072.2015.1012610

Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Rhazinilam-Leuconolam-Leuconoxine Alkaloids from Leuconotis griffithii

Gan CY, Low YY, Thomas NF, Kam TS

J Nat Prod, 2013 May 24;76(5):957-64.
PMID: 23647487 DOI: 10.1021/np400214y

Eight new indole alkaloids (1-8) belonging to the rhazinilam-leuconolam-leuconoxine group, in addition to 52 other alkaloids, were isolated from the stem-bark extract of Leuconotis griffithii, viz., nor-rhazinicine (1), 5,21-dihydrorhazinilam-N-oxide (2), 3,14-dehydroleuconolam (3), and leuconodines A-E (4-8). The structures of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 1, 5, and 7 showed only moderate to weak cytotoxicity toward KB cells (IC50 12-18 μg/mL), while 8 showed moderate activity in reversing MDR in vincristine-resistant KB cells.

Matched MeSH terms: Alkaloids/pharmacology
Reversal of multidrug resistance (MDR) by aspidofractinine-type indole alkaloids

Kam TS, Subramaniam G, Sim KM, Yoganathan K, Koyano T, Toyoshima M, et al.

Bioorg Med Chem Lett, 1998 Oct 06;8(19):2769-72.
PMID: 9873619

A series of indole alkaloids of the aspidofractinine-type was assessed for their potential in reversing MDR in vincristine-resistant KB cells. Of the compounds tested, kopsiflorine, kopsamine, pleiocarpine, 11-methoxykopsilongine, lahadinine A and N-methoxycarbonyl-11,12-methylenedioxy-delta 16,17-kopsinine were found to show appreciable activity.

Matched MeSH terms: Alkaloids/pharmacology*
Quinoline, Indole, and Isogranatanine Alkaloids from Malayan Leuconotis eugeniifolia

Tan YS, Ng MP, Tan CH, Tang WK, Sim KS, Yong KT, et al.

J Nat Prod, 2024 Feb 23;87(2):286-296.
PMID: 38284153 DOI: 10.1021/acs.jnatprod.3c00960

Nine new alkaloids, eugeniinalines A-H (1-8) and (+)-eburnamenine N-oxide (9), comprising one quinoline, six indole, and two isogranatanine alkaloids, were isolated from the stem-bark extract of the Malayan Leuconotis eugeniifolia. The structures and absolute configurations of these alkaloids were established based on the analysis of the spectroscopic data, GIAO NMR calculations, DP4+ probability analysis, TDDFT-ECD method, and X-ray diffraction analysis. Eugeniinaline A (1) represents a new pentacyclic quinoline alkaloid with a 6/6/5/6/7 ring system. Eugeniinaline G (7) and its seco-derivative, eugeniinaline H (8), were the first isogranatanine alkaloids isolated as natural products. The known alkaloids leucolusine (10) and melokhanine A (11) were found to be the same compound, based on comparison of the spectroscopic data of both compounds, with the absolute configuration of (7R, 20R, 21S). Eugeniinalines A and G (1 and 7) showed cytotoxic activity against the HT-29 cancer cell line with IC50 values of 7.1 and 7.2 μM, respectively.

Matched MeSH terms: Indole Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
Psychoactive properties of mitragynine (kratom)

Jansen KL, Prast CJ

J Psychoactive Drugs, 1988 Oct-Dec;20(4):455-7.
PMID: 3072396
Matched MeSH terms: Alkaloids/pharmacology; Secologanin Tryptamine Alkaloids/pharmacology
Pseuduvarines A and B, two new cytotoxic dioxoaporphine alkaloids from Pseuduvaria rugosa

Taha H, Hadi AH, Nordin N, Najmuldeen IA, Mohamad K, Shirota O, et al.

Chem Pharm Bull (Tokyo), 2011;59(7):896-7.
PMID: 21720044

Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC₅₀, 0.9, 21.7, and >50.0 µM, respectively, 2: IC₅₀ >50.0, 15.7, and 12.4 µM, respectively).

Matched MeSH terms: Alkaloids/pharmacology
Protective effects of total alkaloidal extract from Murraya koenigii leaves on experimentally induced dementia

Mani V, Ramasamy K, Ahmad A, Parle M, Shah SA, Majeed AB

Food Chem Toxicol, 2012 Mar;50(3-4):1036-44.
PMID: 22142688 DOI: 10.1016/j.fct.2011.11.037

Dementia is a syndrome of gradual onset and continuous decline of higher cognitive functioning. It is a common disorder in older persons and has become more prevalent today. The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavor that they impart. These leaves have also been proven to have health benefits. In the present study, the effect of total alkaloidal extract from M. koenigii leaves (MKA) on cognitive functions and brain cholinesterase activity in mice were determined. In vitro β-secretase 1 (BACE1) inhibitory activity was also evaluated. The total alkaloidal extract was administered orally in three doses (10, 20 and 30 mg/kg) for 15 days to different groups of young and aged mice. Elevated plus maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam-, scopolamine-, and ageing-induced amnesia served as the interoceptive behavioral models. MKA (20 and 30 mg/kg, p.o.) showed significant improvement in memory scores of young and aged mice. Furthermore, the same doses of MKA reversed the amnesia induced by scopolamine (0.4 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.). Interestingly, the brain cholinesterase activity was also reduced significantly by total alkaloidal extract of M. koenigii leaves. The IC50 value of MKA against BACE1 was 1.7 μg/mL. In conclusion, this study indicates MKA to be a useful remedy in the management of Alzheimer's disease and dementia.

Matched MeSH terms: Alkaloids/pharmacology
Preparation and Preliminary Structure-Activity Relationship Studies of Schwarzinicine A Analogs as Vasorelaxant Agents

Lee FK, Chan NJ, Krishnan P, Datu Abdul Salam DS, Chee XW, Muhamad A, et al.

J Nat Prod, 2024 Apr 26;87(4):675-691.
PMID: 38442031 DOI: 10.1021/acs.jnatprod.3c00707

Schwarzinicines A-D, a series of alkaloids recently discovered from Ficus schwarzii, exhibit pronounced vasorelaxant activity in rat isolated aorta. Building on this finding, a concise synthesis of schwarzinicines A and B has been reported, allowing further investigations into their biological properties. Herein, a preliminary exploration of the chemical space surrounding the structure of schwarzinicine A (1) was carried out aiming to identify structural features that are essential for vasorelaxant activity. A total of 57 analogs were synthesized and tested for vasorelaxant activity in rat isolated aorta. Both efficacy (Emax) and potency (EC50) of these analogs were compared. In addition to identifying structural features that are required for activity or associated with potency enhancement effect, four analogs showed significant potency improvements of up to 40.2-fold when compared to 1. Molecular dynamics simulation of a tetrameric 44-bound transient receptor potential canonical-6 (TRPC6) protein indicated that 44 could potentially form important interactions with the residues Glu509, Asp530, Lys748, Arg758, and Tyr521. These results may serve as a foundation for guiding further structural optimization of the schwarzinicine A scaffold, aiming to discover even more potent analogs.

Matched MeSH terms: Alkaloids/pharmacology
Fulltext Potential role of marine species-derived bioactive agents in the management of SARS-CoV-2 infection

Asif M, Saleem M, Yaseen HS, Yehya AH, Saadullah M, Zubair HM, et al.

Future Microbiol, 2021 Nov;16(16):1289-1301.
PMID: 34689597 DOI: 10.2217/fmb-2021-0024

COVID-19, caused by the SARS-CoV-2 outbreak, has resulted in a massive global health crisis. Bioactive molecules extracted or synthesized using starting material obtained from marine species, including griffithsin, plitidepsin and fingolimod are in clinical trials to evaluate their anti-SARS-CoV-2 and anti-HIV efficacies. The current review highlights the anti-SARS-CoV-2 potential of marine-derived phytochemicals explored using in silico, in vitro and in vivo models. The current literature suggests that these molecules have the potential to bind with various key drug targets of SARS-CoV-2. In addition, many of these agents have anti-inflammatory and immunomodulatory potentials and thus could play a role in the attenuation of COVID-19 complications. Overall, these agents may play a role in the management of COVID-19, but further preclinical and clinical studies are still required to establish their role in the mitigation of the current viral pandemic.

Matched MeSH terms: Alkaloids/pharmacology
Phytochemicals and Potential Therapeutic Targets on Toxoplasma gondii Parasite

Abdullahi SA, Unyah NZ, Nordin N, Basir R, Nasir WM, Alapid AA, et al.

Mini Rev Med Chem, 2020;20(9):739-753.
PMID: 31660810 DOI: 10.2174/1389557519666191029105736

Identification of drug target in protozoan T. gondii is an important step in the development of chemotherapeutic agents. Likewise, exploring phytochemical compounds effective against the parasite can lead to the development of new drug agent that can be useful for prophylaxis and treatment of toxoplasmosis. In this review, we searched for the relevant literature on the herbs that were tested against T. gondii either in vitro or in vivo, as well as different phytochemicals and their potential activities on T. gondii. Potential activities of major phytochemicals, such as alkaloid, flavonoid, terpenoids and tannins on various target sites on T. gondii as well as other related parasites was discussed. It is believed that the phytochemicals from natural sources are potential drug candidates for the treatment of toxoplasmosis with little or no toxicity to humans.

Matched MeSH terms: Alkaloids/pharmacology
Physicochemical Characterization of Mitragyna speciosa Alkaloid Extract and Mitragynine using In Vitro High Throughput Assays

Kong WM, Chik Z, Mohamed Z, Alshawsh MA

Comb Chem High Throughput Screen, 2017;20(9):796-803.
PMID: 29076424 DOI: 10.2174/1386207320666171026121820

AIM AND OBJECTIVE: Mitragynine, a major active alkaloid of Mitragyna speciosa, acts as an agonist on µ-opioid receptors, producing effects similar to morphine and other opioids. It has been traditionally utilized to alleviate opiate withdrawal symptoms. Besides consideration about potency and selectivity, a good drug must possess a suitable pharmacokinetic profile, with suitable absorption, distribution, metabolism, excretion and toxicity (ADME-Tox) profile, in order to have a high chance of success in clinical trials.
MATERIAL AND METHOD: The purity of mitragynine in a Mitragyna speciosa alkaloid extract (MSAE) was determined using Ultra-Fast Liquid Chromatography (UFLC). In vitro high throughput ADMETox studies such as aqueous solubility, plasma protein binding, metabolic stability, permeability and cytotoxicity tests were carried out to analyze the physicochemical properties of MSAE and mitragynine. The UFLC quantification revealed that the purity of mitragynine in the MSAE was 40.9%.
RESULTS: MSAE and mitragynine are highly soluble in aqueous solution at pH 4.0 but less soluble at pH 7.4. A parallel artificial membrane permeability assay demonstrated that it is extensively absorbed through the semi-permeable membrane at pH 7.4 but very poorly at pH 4.0. Both are relatively highly bound to plasma proteins (> 85 % bound) and are metabolically stable to liver microsomes (> 84 % remained unchanged). In comparison to MSAE, mitragynine showed higher cytotoxicity against WRL 68, HepG2 and Clone 9 hepatocytes after 72 h treatment.
CONCLUSION: The obtained ADME and cytotoxicity data demonstrated that both MSAE and mitragynine have poor bioavailability and have the potential to be significantly cytotoxic.

Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
Fulltext Palmatine as an Agent Against Metabolic Syndrome and Its Related Complications: A Review

Ekeuku SO, Pang KL, Chin KY

Drug Des Devel Ther, 2020;14:4963-4974.
PMID: 33235437 DOI: 10.2147/DDDT.S280520

Palmatine is a naturally occurring isoquinoline alkaloid with various pharmacological properties. Given its antioxidant and anti-inflammatory properties, palmatine may be able to impede the effects of metabolic syndrome (MetS) and its related diseases triggered by inflammation and oxidative stress. This review summarises the existing literature about the effects of palmatine supplementation on MetS and its complications. The evidence shows that palmatine could protect against MetS, and cardiovascular diseases, osteoporosis and osteoarthritis, which might be associated with MetS. These protective effects are mediated by the antioxidant and anti-inflammatory properties of palmatine. Although preclinical experiments have demonstrated the efficacy of palmatine against MetS and its related diseases, no human clinical trials have been performed to validate these effects. This research gap should be bridged to validate the efficacy and safety of palmatine supplementation in protecting humans against MetS and its related diseases.

Matched MeSH terms: Berberine Alkaloids/pharmacology*

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