*Article* **Anti-Inflammatory, Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of** *Momordica charantia* **L.**

**Wilmer H. Perera 1, Siddanagouda R. Shivanagoudra 1, Jose L. Pérez 1, Da Mi Kim 2, Yuxiang Sun 2, Guddadarangavvanahally K. Jayaprakasha <sup>1</sup> and Bhimanagouda S. Patil 1,\***


**Abstract:** Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. *Momordica charantia* L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-*O*-β-D-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, **6**) along with 25ξ-isopropenylchole-5(6)-ene-3-*O*-β-D-glucopyranoside (**1**), karaviloside VI (**2**), karaviloside VIII (**3**), momordicoside L (**4**), momordicoside A (**5**) and kuguaglycoside C (**7**) from an Indian cultivar of *Momordica charantia*. At 50 μM compounds, **2**–**6** differentially affected the expression of pro-inflammatory markers *IL-6*, *TNF-α*, and *iNOS*, and mitochondrial marker *COX-2*. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase.

**Keywords:** *Momordica charantia*; cucurbitane-type triterpene glycosides; charantoside XV; α-amylase; α-glucosidase; anti-inflammatory activity; in silico study
