The number of patients with type 2 diabetes mellitus (T2DM) has increased worldwide. Although an instant cure was achieved with the standard treatment acabose, unsatisfactory symptoms associated with cardiovascular disease after acabose administration have been reported. Therefore, it is important to explore new treatments. A Thai folk recipe has long been used for T2DM treatment, and it effectively decreases blood glucose. However, the mechanism of this recipe has never been proven. Therefore, the potential anti-T2DM effect of this recipe, which is used in Thai hospitals, was determined to involve alpha-glucosidase (AG) inhibition with a half maximal inhibitory concentration (IC 50 ). In vitro experiments showed that crude Cinnamomum verum extract (IC 50 ¼ 0.35 AE 0.12 mg/mL) offered excellent inhibitory activity, followed by extracts from Tinospora crispa (IC 50 ¼ 0.69 AE 0.39 mg/ mL), Stephania suberosa (IC 50 ¼ 1.50 AE 0.17 mg/mL), Andrographis paniculate (IC 50 ¼ 1.78 AE 0.35 mg/mL), and Thunbergia laurifolia (IC 50 ¼ 4.66 AE 0.27 mg/mL). However, the potencies of these extracts were lower than that of acabose (IC 50 ¼ 0.55 AE 0.11 mg/mL). Therefore, this study investigated and developed a formulation of this recipe using computational docking. Among 61 compounds, 7 effectively inhibited AG, including chlorogenic acid (IC 50 ¼ 819.07 pM) through 5 hydrogen bonds (HBs) and 2 hydrophobic interactions (HIs); β-sitosterol (IC 50 ¼ 4.46 nM, 6 HIs); ergosterol peroxide (IC 50 ¼ 4.18 nM, 6 HIs); borapetoside D (IC 50 ¼ 508.63 pM, 7 HBs and 2 HIs); borapetoside A (IC 50 ¼ 1.09 nM, 2 HBs and 2 His), stephasubimine (IC 50 ¼ 285.37 pM, 6 HIs); and stephasubine (IC 50 ¼ 1.09 nM, 3 HBs and 4 HIs). These compounds bind with high affinity to different binding pockets, leading to additive effects. Moreover, the pharmacokinetics of six of these seven compounds (except ergosterol peroxide) showed poor absorption in the gastrointestinal tract, which would allow for competitive binding to AG in the small intestine. These results indicate that the development of these 6 compounds into oral antidiabetic agents is promising.
Extracts from Holothuria scabra (HS) have been shown to possess anti-inflammation, anti-oxidant and anti-cancer activities. More recently, it was shown to have neuroprotective potential in Caenorhabditis elegans PD model. Here, we assessed whether HS has neuroprotective and neurorestorative effects on dopaminergic neurons in both mouse and cellular models of PD. We found that both pre-treatment and post-treatment with HS improved motor deficits in PD mouse model induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as determined by grid walk test. This was likely mediated by HS protective and restorative effects on maintaining the numbers of dopaminergic neurons and fibers in both substantia nigra pars compacta (SNpc) and striatum. In a cellular model of PD, HS significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of DAergic-like neurons differentiated from SH-SY5Y cells by enhancing the expression of Bcl-2, suppressing the expression of cleaved Caspase 3 and preventing depolarization of mitochondrial membrane. In addition, HS could stimulate the expression of tyrosine hydroxylase (TH) and suppressed the formation of α-synuclein protein. Taken together, our in vivo and in vitro findings suggested that HS is an attractive candidate for the neuroprotection rather than neurorestoration in PD.
Background Lysiphyllum strychnifolium (Craib) A. Schmitz, a traditional Thai medicinal plant, is mainly composed of polyphenols and flavonoids and exhibits several pharmacological activities, including antioxidant, anticancer, antimicrobial, and antidiabetic activities. However, the mechanism by which pure compounds from L. strychnifolium inhibit glucose catalysis in the small intestine and their effect on the glucose transporter remain unknown. Methods The objectives of this research were to examine the effect of 3,5,7-trihydroxychromone-3-O-𝛼-L-rhamnopyranoside (compound 1) and 3,5,7,3’,5’-pentahydroxy-flavanonol-3-O-𝛼-L-rhamnopyranoside (compound 2) on the inhibition of α-amylase and α-glucosidase, as well as glucose transporters, such as sodium-glucose cotransporter 1 (SGLT1), glucose transporter 2 (GLUT2), and glucose transporter 5 (GLUT5), using Caco-2 cells as a model of human intestinal epithelial cells. Additionally, the binding affinity and interaction patterns of compounds against two receptor proteins (SGLT1 and GLUT2) were determined for the first time utilizing a molecular docking approach. Results In the α-amylase inhibition assay, a concentration-dependent inhibitory response was observed against the enzyme. The results indicated that compound 1 inhibited α-amylase activity in a manner similar to that of acarbose (which exhibit IC50 values of 3.32 ± 0.30 µg/mL and 2.86 ± 0.10 µg/mL, respectively) in addition to a moderate inhibitory effect for compound 2 (IC50 = 10.15 ± 0.53 µg/mL). Interestingly, compounds 1 and 2 significantly inhibited α-glucosidase and exhibited better inhibition than that of acarbose, with IC50 values of 5.35 ± 1.66 µg/mL, 510.15 ± 1.46 µg/mL, and 736.93 ± 7.02 µg/mL, respectively. Additionally, α-glucosidase activity in the supernatant of the Caco-2 cell monolayer was observed. In comparison to acarbose, compounds 1 and 2 inhibited α-glucosidase activity more effectively in Caco-2 cells without cytotoxicity at a concentration of 62.5 µg/mL. Furthermore, the glucose uptake pathways mediated by SGLT1, GLUT2, and GLUT5- were downregulated in Caco-2 cells treated with compounds 1 and 2. Additionally, molecular modeling studies revealed that compounds 1 and 2 presented high binding activity with SGLT1 and GLUT2. Conclusion In summary, our present study was the first to perform molecular docking with compounds present in L. strychnifolium extracts. Our findings indicated that compounds 1 and 2 reduced glucose uptake in Caco-2 cells by decreasing the expression of glucose transporter genes and inhibiting the binding sites of SGLT1 and GLUT2. Therefore, compounds 1 and 2 may be used as functional foods in dietary therapy for postprandial hyperglycemia modulation of type 2 diabetes.
Prostate cancer is the second-leading cause of cancer-related deaths in males [1]. After androgen deprivation therapy, prostate cancer inevitably develops into castration-resistant prostate cancer (CRPC) which eventually metastasizes to many vital organs, including bone, brain, liver, and lung [2,3]. Although there are numerous chemotherapeutic agents being used against the advanced stage of prostate cancer, most patients usually end up in resistance to these drugs which results in poor prognosis and death [2]. One way to circumvent this undesirable outcome is using functional foods or nutraceuticals as anti-CRPC agents.Cancer cells possess specific characteristics that allow them to survive. These are uncontrolled growth, abilities to avoid apoptosis, and metastasis to various other organs [4]. Reactive oxygen species (ROS) are key molecules that trigger various signaling transduction pathways [5,6]. Excessive ROS generation causes oxidative stress and damage to a vital organelle in the cells which leads to cellular apoptosis [5]. Additionally, ROS also plays an important role in mediating tumor cell migration and invasion [7]. ROS can act in cooperation with MAPK pathway, especially JNK and p38 [8]. Therefore, natural products or nutraceutics that can result in apoptosis and inhibition of metastasis via the ROS axis may be an alternative treatment against cancer cells [9].More than half of modern chemotherapeutic drugs used for cancer treatment are developed or derived from natural products [4]. Marine animals are currently considered as a tremendous source of bioactive compounds which have a wide range of biological properties, including anti-oxidant, anti-bacteria, anti-inflammation, and anti-tumor [10,11]. Sea cucumber, Holothuria scabra, especially its body wall, is a nutritious echinoderm. Previous reports demonstrated that it contains a variety of pharmacologically active molecules, particularly Sea cucumber, Holothuria scabra, is a well-known traditional Asian medicine that has been used for suppressing inflammation, promoting wound healing, and improving immunity. Moreover, previous studies demonstrated that the extract from H. scabra contains many bioactive compounds with potent inhibitory effect on tumor cell survival and progression. However, the effect of the methanolic extract from the body wall of H. scabra (BWMT) on human prostate cancer cells has not yet been investigated. In this study, we aimed to investigate the effects and underlying mechanism of BWMT on prostate cancer cell viability and metastasis. BWMT was obtained by maceration with methanol. The effect of BWMT on cell viability was assessed by MTT and colony formation assays. The intracellular ROS accumulation was evaluated using a DCFH-DA fluorescence probe. Hoechst 33342 staining and Annexin V-FITC/PI staining were used to examine the apoptotic-inducing effect of the extract. A transwell migration assay was performed to determine the anti-metastasis effect. BWMT significantly reduced cell viability and triggered cellular apoptosis by ...
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