**1. Introduction**

The genus *Momordica* L., with around 59 species, is one of the most abundant genera in the Cucurbitaceae family. *Momordica charantia* L. is a taxon extensively studied for its antidiabetic properties [1]. Two varieties have been taxonomically identified: *M. charantia* L. (var. *muricata* (Willd.) Chakrav. and var. *charantia*) [1]. The *muricata* variety produces small size fruits, whereas *charantia* typically produces larger fruits [1]. Several phenotypes of *M. charantia* var. *charantia* appear in nature, displaying noteworthy differences in fruit size and shape. The most common fruit from the Indian cultivar has a greenish color, a narrower shape, and a serrated surface. *M. charantia* var. *charantia* L. is commonly consumed in traditional Asian cuisines and is well-known for its unique taste and flavor [2,3].

Cucurbitane-type triterpenes are the most representative sub-class of compounds in *M. charantia*, and some investigations suggest that they are responsible for their antidiabetic property [4,5]. More than 270 cucurbitane-type triterpenes have been isolated from different plant organs from 1980 to date. However, these compounds are found in very

#### **Citation:** Perera, W.H.;

Shivanagoudra, S.R.; Pérez, J.L.; Kim, D.M.; Sun, Y.; K. Jayaprakasha, G.; S. Patil, B. Anti-Inflammatory, Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of *Momordica charantia* L. *Molecules* **2021**, *26*, 1038. https://doi.org/10.3390/molecules 26041038

Academic Editors: Ilias Muhammad and Nanayakkara Dhammika Received: 18 January 2021 Accepted: 12 February 2021 Published: 16 February 2021

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

low concentration and their composition has been reported to vary between cultivars. Our comprehensive survey of the literature indicates that the Indian phenotype has received less attention than the Chinese or Sri Lanka phenotypes. Octonorcucurbitacins A, B and C (342 Da) are the smallest cucurbitane-type compounds reported from *M. charantia,* whereas momordicoside T (1110 Da) the largest one with four sugar units, one glucose linked at position C-25, two glucose units, and one xylose attached at C-3 as follows: -Glc[Glc(1- 4)]Xyl(1–4) [4–6]. Additionally, several aglycones, mono, di, and tri-glycoside triterpene derivatives have also been isolated from bitter melon. The glycosidic moieties attached to these triterpenes typically consist of D series of allose, galactose, glucose and xylose monosaccharide units, mainly at positions C-23 and C-25 of the side chain, and C-3 and C-7 of the A and B rings, respectively [4,7–9].

Many purified compounds, as well as crude extracts, have been screened in response to various ethnomedicinal claims, concluding that bitter melon may play a potential role in the management of various chronic diseases by working as an antidiabetic, antioxidant, antiviral, antiobesity, and anticancer agent among others [8–14]. Moreover, some studies have been conducted in fruit, seeds, and leaves showing hypoglycemic activity in both diabetic animal and human models [15,16]. Thus, *M. charantia* var. *charantia* stands out as a promising natural alternative to reduce the risk and/or manage diabetes mellitus type II [17].

Diabetes is a chronic disease that affects millions of people worldwide. Therefore, it is vital to find new natural prevention and management strategies for this disease and related complications. Results from our previous studies indicated that cucurbitane-type triterpenoids isolated from Chinese cultivar might modulate biological activities involved in the pathogenicity of diabetes [18,19]. Due to these molecules structural complexity, much more work is warranted to test biological activities and better understand the structure-activity relationship. Therefore, herein we describe the isolation and structure elucidation of a new cucurbitane-type triterpene together with six known compounds from acetone extract of the Indian cultivar of *M. charantia*. The anti-inflammatory activity of purified compounds using lipopolysaccharide (LPS)-activated RAW264.7 macrophage cells, inhibition of the α-amylase, and α-glucosidase enzymes were presented. Furthermore, the molecular interaction of purified compounds with α-amylase and α-glucosidase enzymes was also studied using *in silico* molecular docking.
