Search

This study systematically explores a green extraction process of T. crispa stems to selectively isolate therapeutic compounds, borapetoside C (BPC) and magnoflorine (MGF), recognized for their anti-diabetic properties. In agreement with Hansen solubility parameters prediction, H2O and EtOH were found to be suitable solvents for extraction of BPC and MGF, respectively, resulting in 33 % and 45 % extractabilities after 60 min. Further investigations demonstrated considerable increase in BPC extractability using 20 % EtOH:H2O mixture at 40 °C, with complete extraction achieved after 60 min. While for MGF, pure-EtOH at 40 °C, was the most suitable solvent, showing the highest selectivity and complete extraction after 100 min. The BPC-rich extract from 20 % EtOH:H2O exhibited higher anti-diabatic activity (IC50 = 0.63 ± 0.03 and 0.72 ± 0.04 mg/mL, respectively, for α-glucosidase and α-amylase enzymes inhibition activity), and considerably lower cytotoxicity to L6 and HepG2 cells, with IC50 = 0.26 ± 0.16 and 0.24 ± 0.02 mg/mL, respectively, compared with the MGF-rich extract obtained with pure-EtOH. Based on these results, a sequential extraction scheme was proposed involving initial pure-EtOH extraction to selectively and completely remove MGF, followed by extraction with a 20 % EtOH:H2O mixture to recover the remaining BPC, which was approximately 80 % of the BPC originally present. The obtained MGF-free BPC-rich extract showed significantly lower cytotoxicity (IC50 = 0.31 ± 0.06 mg/mL against L6 cell) and higher enzyme inhibition activities (IC50 = 0.53 ± 0.32 and 0.52 ± 0.02 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), comparable to acarbose (IC50 = 0.43 ± 0.02 and 0.83 ± 0.03 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), the result that potentially leads to the development of a promising industrial process to harness T. crispa for diabetes prevention and treatment.

In this study, pressurized hot water extraction (PHWE) was evaluated for the recovery of anti-diabetic borapetoside C (BPC) from T. crispa stems. The maximum BPC extraction efficiency obtained at 100 ˚C, 2.5 MPa and 5.0 mL/min was considerably higher than that obtained by the conventional methods. Under optimized conditions, one-site kinetic desorption model could most accurately describe the PHWE behavior, suggesting an intra-particle diffusion-controlled mechanism. The undesirable compounds in the extract were further removed by micelle-mediated separation (MMS), in which Tween 80 was added, followed by NaCl addition and slight temperature increase to induce phase separation. At the most suitable MMS condition, with 0.028 mM Tween 80, 0.4 M NaCl, at 85 ˚C, the majority (87 %) of BPC could be recovered in the aqueous phase after 40 min. After MMS, the resulting extract exhibited low cytotoxicity against L6 and HepG2 cells while maintaining significant α-glucosidase and α-amylase inhibition activities. [Display omitted] • Pressurized hot water extraction (PHWE) of BPC from T. crispa was optimized. • Optimal PHWE conditions were found to be 100 °C, 5 mL/min and 2.5 MPa. • The optimized PHWE conditions accurately fit the one-site kinetic desorption model. • Micelle-mediated separation with Tween 80 selectively removes undesirable compounds from PHWE extracts. • PHWE/MMS extracts exhibit comparable activity to acarbose with low toxicity to L6 cells. [ABSTRACT FROM AUTHOR]

[Display omitted] This study systematically explores a green extraction process of T. crispa stems to selectively isolate therapeutic compounds, borapetoside C (BPC) and magnoflorine (MGF), recognized for their anti-diabetic properties. In agreement with Hansen solubility parameters prediction, H 2 O and EtOH were found to be suitable solvents for extraction of BPC and MGF, respectively, resulting in 33 % and 45 % extractabilities after 60 min. Further investigations demonstrated considerable increase in BPC extractability using 20 % EtOH:H 2 O mixture at 40 °C, with complete extraction achieved after 60 min. While for MGF, pure-EtOH at 40 °C, was the most suitable solvent, showing the highest selectivity and complete extraction after 100 min. The BPC-rich extract from 20 % EtOH:H 2 O exhibited higher anti-diabatic activity (IC 50 = 0.63 ± 0.03 and 0.72 ± 0.04 mg/mL, respectively, for α-glucosidase and α-amylase enzymes inhibition activity), and considerably lower cytotoxicity to L6 and HepG2 cells, with IC 50 = 0.26 ± 0.16 and 0.24 ± 0.02 mg/mL, respectively, compared with the MGF-rich extract obtained with pure-EtOH. Based on these results, a sequential extraction scheme was proposed involving initial pure-EtOH extraction to selectively and completely remove MGF, followed by extraction with a 20 % EtOH:H 2 O mixture to recover the remaining BPC, which was approximately 80 % of the BPC originally present. The obtained MGF-free BPC-rich extract showed significantly lower cytotoxicity (IC 50 = 0.31 ± 0.06 mg/mL against L6 cell) and higher enzyme inhibition activities (IC 50 = 0.53 ± 0.32 and 0.52 ± 0.02 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), comparable to acarbose (IC 50 = 0.43 ± 0.02 and 0.83 ± 0.03 mg/mL for α-glucosidase and α-glucosidase enzymes inhibition activity), the result that potentially leads to the development of a promising industrial process to harness T. crispa for diabetes prevention and treatment. [ABSTRACT FROM AUTHOR]

Melanoma,also known as a ' black tumor ', begins in the melanocytes when cells (that produce pigment) grows out of control. Immunological dysregulation, which raises the risk for multiple illnesses, including melanoma, may be influenced by stress tiggered through viral infection, long term effects of ultraviolet radiation, environmental pollutants etc. Borapetoside C is one of the phytoconstituents from Tinospora crispa , and its biological source has been reported for its antistress property. Network pharmacology and KEGG pathway analysis of borapetoside C-regulated proteins were conducted to identify the hub genes involved in melanoma development. Further, a molecular docking was performed between borapetoside C and targets involved in melanoma. Further, the top 3 complexes were selected based on the binding energy to conduct molecular dynamics simulations to evaluate the stability of ligand-protein complex followed by principal component analysis and dynamic cross-correlation matrix. In addition, borapetoside C was also screened for its pharmacokinetics and toxicity profile. Network Pharmacology studies and KEGG pathway analysis revealed 8 targets involved in melanoma. Molecular docking between borapetoside C and targets involved in melanoma identified 3 complexes with minimum binding i.e. borapetoside C- MAP2K1 , MMP9 , and EGFR . Further, molecular dynamics simulations showed a stable complex of borapetoside C with MMP9 and EGFR . The present study suggested that borapetoside C may target MMP9 and EGFR to possess an anti-melanoma property. This finding can be useful in developing a novel therapeutic agent against melanoma from a natural source.Communicated by Ramaswamy H. Sarma.

Tinospora crispa (Borapet or Wan kab hoi yai) is a climbing plant belonging to family Menispermaceae. In traditional medicine, an extract from the stems of T. crispa has been used for anti-hyperglycemic activity. The mechanisms of the anti-hyperglycemic actions of T. crispa are due to the stimulation of insulin secretion, enhancement of glucose utilization in peripheral tissues and reduction of hepatic gluconeogenesis. Borapetoside A and C are active ingredients for lower plasma glucose. In human studies, T. crispa extract possesses a significant anti-hyperglycemic effect in metabolic syndrome but this effect is abolished in type 2 diabetes mellitus. More clinical studies are recommended to evaluate the beneficial effect of T. crispa in human models.

Abstract: Diabetes mellitus (DM) often leads to disability from vascular complications and neurological complications. Tinospora crispa has been widely used in Asia and Africa as a remedy for diabetes and other diseases. In this study, we investigated the hypoglycemic actions of borapetoside C isolated from T. crispa, and the mechanisms underlying its actions. Acute treatment with borapetoside C (5mg/kg, i.p.) attenuated the elevated plasma glucose induced by oral glucose in normal and type 2 DM (T2DM) mice. Compared to the effect of injected insulin (0.5IU/kg), borapetoside C caused a more prominent increase of glycogen content in skeletal muscle of T2DM mice, but a less increase in type 1 DM (T1DM) mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, i.p.) plus insulin enhanced insulin-induced lowering of the plasma glucose level and insulin-induced increase of muscle glycogen content. Continuous treatment with 5mg/kg borapetoside C (twice daily) for 7days increased phosphorylation of insulin receptor (IR) and protein kinase B (Akt) as well as the expression of glucose transporter-2 (GLUT2) in T1DM mice. Combined treatment of a low dose borapetoside C (0.1mg/kg, twice daily) plus insulin for 7days enhanced insulin-induced IR and Akt phosphorylation and GLUT2 expression in the liver of T1DM mice. This study proved that borapetoside C can increase glucose utilization, delayed the development of insulin resistance and enhanced insulin sensitivity. The activation of IR-Akt-GLUT2 expression and the enhancement of insulin sensitivity may contribute to the hypoglycemic action of borapetoside C in diabetic mice. [Copyright &y& Elsevier]

• A validated UHPLC-UV-MS method developed for distinguishing T. crispa from related species. • Intra- and inter-day RSD for replicates were 0.9 – 6.8 % and 1.2 – 9.1 %, respectively. • Limits of detection ranged from 0.3 to 10 μg/mL. • The data suggests two dietary supplements claim to contain T. cordifolia as mislabeled. Tinospora species are morphologically similar. Several cases of human toxicity have been reported in association with T. crispa. A chemical fingerprint was developed to differentiate T. crispa from its closely related species and to quantitate its major furanoditerpenes namely as borapetosides B, C and F. The rapid, sensitive and repeatable method was established using ultra–high performance liquid chromatography coupled with photodiode array and single quadrupole electrospray mass spectrometry detectors using a flavonoid, two alkaloids, an amide and six diterpenoids. Qualitative and quantitative determination was performed by UHPLC-UV and confirmed by MS. The intra-day RSD for replicates was between 0.9 and 6.8% and inter-day RSD was between 1.2 and 9.1%. Recovery was 97–103 %. The method is useful to achieve decisiveness in not only identifying but also differentiating T. crispa from T. sinensis and other closely related Tinospora species. Seventeen Tinospora plant samples and seventeen dietary supplements claiming T. crispa , T. sinensis and T. cordifolia were analyzed. The newly developed and validated method successfully resulted in the conclusive identification of two dietary supplements to be mislabeled. [ABSTRACT FROM AUTHOR]