Artemisia annua L. Extracts Improved Insulin Resistance via Changing Adiponectin, Leptin and Resistin Production in HFD/STZ Diabetic Mice

Abstract

Objectives: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods: We divided 60 mice into 12 groups (n = 5 per group): control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.

Inhibition of TNF-α Oncogene Expression by Artemisia Annua L. Extract Against Pioglitazone Side Effects in Male Albino Mice

“…In testis tissues, the results of Artemisia annua showed normal spermatic tubules with active spermatogenesis reaching spermatozoa stage in all treated and non-treated animal groups. In the previous studies, the histopathology indicating that the liver was not adversely affected by EAA further confirmed the earlier statements that EAA may not be toxic to the liver [ 19 , 20 ]. While, [ 22 ] has found that the acute administration of large doses of pioglitazone (Actos drug) caused ventricular hypertrophy with congestion of liver in mice which can happen with accidental over dose of pioglitazone in patients.…”

“…In related previous studies, [ 19 ] has found no changes in the liver (ALT and AST) and kidney (urea and Creatinine) functions in all the EAA-treated ( Artemisia Annua Ethanol extract) groups compared to the control group and the author recommended that EAA treatment may not predispose the users of this plant to hepatotoxicity and renal dysfunction. Concerning glucose, different types of AA extracts were used by [ 20 ] to improve insulin resistance through reduction of TNF-alpha. These previous results confirm our findings that higher levels of bioactive components might be present in the higher concentrations of Artemisia extracts.…”

“…[ 21 , 23 ] have found that therapy duration and cumulative dose of pioglitazone (Actos drug) increased the risk of developing chronic kidney disease. While, [ 20 ] has found that EAA may not be toxic to the kidney. In studies by [ 24 , 25 ], sub-chronic use of pioglitazone (Actos drug) may lead to bladder affection, however, current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner.…”

Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1β/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats

“…The treatment of C. papaya brought down the levels of these adipocytokines close to normalcy, such as that of standard drug treated group. Likewise, Ghanbari, et al [51] reported that aqueous and alcoholic extracts of Artemisia annua L. augmented the insulin resistance in high fat diet-streptozotocin induced T2DM mice with a surge in adiponectin and diminution in leptin and resistin production in fat cells. Ansari et al and his co-workers reported in their work the effect of synthesized gold nanoparticles from Smilax glabra that modulated the levels of serum leptin and adiponectin in high fat diet-streptozotocin induced rat models [52].…”

Medicinal plant-derived mtDNA via nanovesicles induces the cGAS-STING pathway to remold tumor-associated macrophages for tumor regression

“…Artemisinin has been recognized as a potent and effective antimalarial drug that has been widely applied in the world [43]. Beyond anti-parasite activity, artemisinin and its derivatives exhibit the therapeutic potentials for viral infections, inflammatory disease, autoimmune diseases and cancer [44][45][46][47]. Also, the extracts of Artemisia annua, particularly artemisinin and flavonoids, have been reported to have numerous pharmacological properties [48,49].…”