Mitragyna speciosa is a tropical plant with narcotic effects. The antinociceptive effects of its crude extracts, bioactive compounds and structurally modified derivatives have been examined in rodent models. This review aims to summarize the evidence on the antinociceptive effects of M. speciosa and its derivatives and explore whether they can offer an alternative to morphine in pain management. Methanolic and alkaloid extracts of M. speciosa were shown to attenuate the nociceptive response in rodents. Mitragynine and 7-hydroxymitragynine offered better antinociceptive effects than crude extracts. Structurally modified derivatives of 7-hydroxymitragynine, such as MGM-9, MGM- 15, MGM-16, demonstrated superior antinociceptive effects compared to morphine. M. speciosa and its derivatives mainly act on the opioid receptor, but receptor subtypes specificity differs between each compound. The tolerance and adverse side effects of M. speciosa and its derivatives are similar with morphine. The affinity of MGM-9 on kappa-opioid receptor could potentially limit the effects of drug dependence. In conclusion, M speciosa derivatives can offer alternatives to morphine in controlling chronic pain. Structural modification of mitragynine and 7-hydroxymitragynine can generate compounds with higher potency and lesser side-effects. Human clinical trials are required to validate the use of these compounds in clinical setting.
Bisphenol A (BPA) is an endocrine disruptor which can bind to the oestrogen receptor. It also possesses oestrogenic, antiandrogenic, inflammatory and oxidative properties. Since bone responds to changes in sex hormones, inflammatory and oxidative status, BPA exposure could influence bone health in humans. This review aimed to summarize the current evidence on the relationship between BPA and bone health derived from cellular, animal and human studies. Exposure to BPA (0.5-12.5 µM) decreased the proliferation of osteoblast and osteoclast precursor cells and induce their apoptosis. Bisphenol AF (10 nM) enhanced transforming growth factor beta signalling but bisphenol S (10 nM) inhibited Wnt signalling involved in osteoblast differentiation in vitro. In animals, BPA and its derivatives demonstrated distinct effects in different models. In prenatal/postnatal exposure, BPA increased femoral bone mineral content in male rats (at 25 ug/kg/day) but decreased femoral mechanical strength in female mice (at 10 µg/kg/day). In oestrogen deficiency models, BPA improved bone mineral density and microstructures in aromatase knockout mice (at very high dose, 0.1% or 1.0% w/w diet) but decreased trabecular density in ovariectomized rats (at 37 or 370 ug/kg/day). In contrast, bisphenol A diglycidyl ether (30 mg/kg/day i.p.) improved bone health in normal male and female rodents and decreased trabecular separation in ovariectomized rodents. Two cross-sectional studies have been performed to examine the relationship between BPA level and bone mineral density in humans but they yielded negligible association. As a conclusion, BPA and its derivatives could influence bone health and a possible gender effect was observed in animal studies. However, its effects in humans await verification from more comprehensive longitudinal studies in the future.
The crystal and molecular structures of two ReI tricarbonyl complexes, namely fac-tricarbonylchlorido[1-(4-fluorocinnamoyl)-3-(pyridin-2-yl-κN)pyrazole-κN2]rhenium(I), [ReCl(C17H12FN3O)(CO)3], (I), and fac-tricarbonylchlorido[1-(4-nitrocinnamoyl)-3-(pyridin-2-yl-κN)pyrazole-κN2]rhenium(I) acetone monosolvate, [ReCl(C17H12ClN4O3)(CO)3]·C3H6O, (II), are reported. The complexes form centrosymmetric dimers that are linked into one-dimensional columns by C-H...Cl and N-O...H interactions in (I) and (II), respectively. C-H...Cl interactions in (II) generate two R21(7) loops that merge into a single R21(10) loop. These interactions involve the alkene, pyrazole and benzene rings, hence restricting the ligand rotation and giving rise to a planar conformation. Unlike (II), complex (I) exhibits a twisted conformation of the ligand and a pair of molecules forms a centrosymmetric dimer with an R22(10) loop via C-H...O interactions. The unique supramolecular structures of (I) and (II) are determined by their planarity and weak interactions. The planar conformation of (II) provides a base for appreciable π-π stacking interactions compared to (I). In addition, an N-O...π interaction stabilizes the supramolecular structure of (II). We report herein the first n→π* interactions of ReI tricarbonyl complexes, which account for 0.33 kJ mol-1. Intermolecular C-H...Cl and C-H...O interactions are present in both complexes, with (II) showing a greater preference for these interactions compared to (I), with cumulative contributions of 48.7 and 41.5%, respectively. The influence of inductive (fluoro) and/or resonance (nitro) effects on the π-stacking ability was further supported by LOLIPOP (localized orbital locator-integrated π over plane) analysis. The benzene ring of (II) demonstrated a higher π-stacking ability compared to that of (I), which is supported by the intrinsic planar geometry. The HOMA (harmonic oscillator model of aromaticity) index of (I) revealed more aromaticity with respect to (II), suggesting that NO2 greatly perturbed the aromaticity. The Hirshfeld fingerprint (FP) plots revealed the preference of (II) over (I) for π-π contacts, with contributions of 6.8 and 4.4%, respectively.
The fundamental mechanism of biochemistry lies on the reaction kinetics, which is determined by the reaction pathways. Interestingly, the reaction pathway is a challenging concept for undergraduate students. Experimentally, it is difficult to observe, and theoretically, it requires some degree of physics knowledge, namely statistical and quantum mechanics. However, students can utilize computational methods to study the reaction kinetics without paying too much attention but not wholly neglecting the comprehension of physics. We hereby provided an approach to study the reaction kinetics based on density-functional calculations. We particularized the study of the isomerization case involving five molecules at three different temperatures and emphasized the importance of the transition state in the study of reaction kinetics. The results we presented were in good agreement with the experiments and provided useful insights to assist students in the application of their knowledge into their research.
Enzymatic treatment on lignocellulosic biomass has become a trend in preparing nanocellulose (NC), but the process must be optimized to guarantee high production yield and crystallinity. This study offers insights into an innovative protocol using cultivated fungal cellulase and xylanase to improve NC production from raw oil palm leaves (OPL) using five-factor-four-level Taguchi orthogonal design for optimizing parameters, namely substrate and enzyme loading, surfactant concentration, incubation temperature and time. Statistical results revealed the best condition for producing NC (66.06 % crystallinity, 43.59 % yield) required 10 % (w/v) substrate, 1 % (v/v) enzyme, 1.4 % (w/v) Tween-80, with 72-h incubation at 30 °C. Likewise, the highest sugar yield (47.07 %) was obtained using 2.5 % (w/v) substrate, 2.0 % (v/v) enzyme, 2.0 % (w/v) Tween-80, with 72-h incubation at 60 °C. The auxiliary enzymes used in this study, i.e., xylanase, produced higher crystallinity NC, showing widths between 8 and 12 nm and lengths >1 μm and sugars at 47.07 % yield. Thus, our findings proved that optimizing the single-step enzymatic hydrolysis of raw OPL could satisfactorily produce relatively crystalline NC and sugar yield for further transformation into bio-nanocomposites and biofuels. This study presented a simple, innovative protocol for NC synthesis showing characteristics comparable to the traditionally-prepared NC, which is vital for material's commercialization.
Adsorbates coverage plays a crucial role in a catalysis reaction. In hydrodeoxygenation (HDO), which involves high hydrogen pressure, hydrogen coverage on the surface may affect the adsorption of other adsorbates. The HDO is used in green diesel technology to produce clean and renewable energy from organic compounds. This motivates us to study the hydrogen coverage effect on methyl formate adsorption on MoS2 as a model case of the actual HDO. We calculate the methyl formate adsorption energy as a function of hydrogen coverage using density functional theory (DFT) and then comprehensively analyze the physical origin of the results. We find that methyl formate can have several adsorption modes on the surface. The increased hydrogen coverage can stabilize or destabilize these adsorption modes. However, finally, it leads to convergence at high hydrogen coverage. We extrapolated the trend further and concluded that some adsorption modes might not exist at high hydrogen coverage, while others remain.
Postmenopausal women are susceptible to osteoporosis and osteoarthritis. Tocotrienol, a bone-protective nutraceutical, is reported to prevent osteoarthritis in male rats. However, its efficacy on joint health in oestrogen deficiency has not been validated. Besides, data on the use of emulsification systems in enhancing bioavailability and protective effects of tocotrienol are limited. Ovariectomised adult female Sprague-Dawley rats (3 months old) were treated with refined olive oil, emulsified (EPT, 100 mg/kg/day with 25% vitamin E content), non-emulsified palm tocotrienol (NEPT, 100 mg/kg/day with 50% vitamin E content) and calcium carbonate (1% w/v in drinking water) plus glucosamine sulphate (250 mg/kg/day) for 10 weeks. Osteoarthritis was induced with monosodium iodoacetate four weeks after ovariectomy. Baseline control was sacrificed upon receipt, while the sham group was not ovariectomised and treated with refined olive oil. EPT and NEPT prevented femoral metaphyseal and subchondral bone volume decline caused by ovariectomy. EPT decreased subchondral trabecular separation compared to the negative control. EPT preserved stiffness and Young's Modulus at the femoral mid-shaft of the rats. Circulating RANKL was reduced post-treatment in the EPT group. Joint width was reduced in all the treatment groups vs the negative control. The EPT group's grip strength was significantly improved over the negative control and NEPT group. EPT also preserved cartilage histology based on several Mankin's subscores. EPT performed as effectively as NEPT in preventing osteoporosis and osteoarthritis in ovariectomised rats despite containing less vitamin E content. This study justifies clinical trials for the use of EPT in postmenopausal women with both conditions.
Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug-drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC50 = 0.0130 ± 0.0002 μM) and the K1 strain (EC50 = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.