Oleanolic acid improves hepatic insulin resistance via antioxidant, hypolipidemic and anti-inflammatory effects

A Synthetic-Biology-Inspired Therapeutic Strategy for Targeting and Treating Hepatogenous Diabetes

“…56,57 As a natural triterpenoid widely found in several dietary and medicinal plants (e.g., Olea europaea, Viscum album L., or Aralia chinensis L.), OA has been used in Chinese medicine for the treatment of liver disorders for over 20 years, and commercial OA tablets are available as OTC drugs in Chinese pharmacies for the treatment of acute and chronic hepatitis infections. 30,58 Although they are slow-acting, herbal medicines and medical nutrition therapies are recommended for liver disease patients over pharmacotherapies that utilize chemically synthesized drugs, because the former elicit milder metabolic burdens on a defective liver during the unavoidable hepatic first pass of xenobiotics. 7,53,59 Synthetic biology, which is the science of reassembling characterized, optimized, and cataloged biological building blocks to engineer designer cells to solve predetermined problems in biotechnology and medicine, 32 continually leads to novel therapeutic strategies for treating complex multifactorial diseases.…”

“…In this work, we engineered a synthetic therapeutic designer cell that compensates for the intrinsically slowacting character of OA-based monotherapies. OA and GLP-1 share similar pharmacological activities in attenuating IR, liver dysfunction, and glucose intolerance, 21,30 and a synthetic OA-triggered shGLP-1-expressing device implanted into mice with hepatogenous diabetes enabled a dramatic amplification of the therapeutic effect at the same OA dosage. Only the combined action of OA administration triggering in vivo shGLP-1 secretion was able to attenuate many disease-specific metabolic failures of hepatogenous diabetes over 15 days ( Figure 7); the administration of OA or shGLP-1 alone failed to achieve rapid therapeutic effects.…”

“…Currently, its hepatoprotective, anti-inflammatory, and antidiabetic functions as active ingredients in complementary and alternative medicine (CAM) are also gaining clinical acceptance. [29][30][31] When implanting immunoprotective microcapsules containing OA-regulated short human GLP-1 (shGLP-1)-expressing cells into a mouse model of hepatogenous diabetes, only the combined action of OA administration with shGLP-1 secretion led to the rapid and simultaneous attenuation of many disease-specific metabolic failures such as glucose intolerance, IR, hyperglycemia, dyslipidemia, and excessive liver enzyme levels ( Figure 1). Furthermore, a doxycycline (Dox)-induced regulatory element integrated into the circuit enabled the rapid and on-demand termination of transcription, which provided an increased control capacity for unforeseeable scenarios in vivo.…”

Antidiabetic plants improving insulin sensitivity

“…Stimulates the insulin signalling and inhibits gluconeogenesis, increases the insulin-sensitive glucose transporter GLUT4 mRNA as well as its protein expression in diabetic rats and ameliorates glucose transport [63] 31…”

“…Crocus sativus Iridaceae C2C12 cells Enhances glucose uptake and the phosphorylation of AMPK/ACC and MAPKs [63] 32 Cryptolepis sanguinolenta Apocynaceae Type 2 diabetic mice Stimulates glucose uptake [64] 33 Curcuma comosa Zingiberaceae Ovariectomized rats Enhances insulin-mediated glucose uptake in skeletal muscle and increases muscle GLUT4 protein levels [65] 34 Cyclea peltata Menispermaceae Type 2 diabetic rats Improves glycogen in peripheral tissue such as skeletal muscle [66] 35 Dryopteris fragrans Dryopteridaceae Streptozotocin rats Improves glucose utilization and insulin resistance [67] 36 Echinacea purpurea Compositae Cultured adipocytes Activates PPARγ and increased insulin-stimulated glucose uptake [68] 37 Elaeis guineensis Arecaceae Healthy adults with pre-diabetes…”