**1. Introduction**

Lichens are structurally complex and self-sustaining unique consortia comprised of a fungus host (mycobiont) living with algae or cyanobacteria (photobiont partner) in the framework of a unique symbiotic type of relationship. In recent years, much attention has been paid to the biological roles of lichen metabolites because of their potential applications in perfumery, cosmetics, creative crafts, the dye industry, and the pharmaceutical sector [1,2]. Moreover, many lichens and their extracts and metabolites have been utilized

**Citation:** Kumar, T.K.; Siva, B.; Anand, A.; Anusha, K.; Mohabe, S.; Reddy, A.M.; Le Devehat, F.; Tiwari, A.K.; Boustie, J.; Babu, K.S. Comprehensive Lichenometabolomic Exploration of *Ramalina conduplicans* Vain Using UPLC-Q-ToF-MS/MS: An Identification of Free Radical Scavenging and Anti-Hyperglycemic Constituents. *Molecules* **2022**, *27*, 6720. https://doi.org/10.3390/ molecules27196720

Academic Editor: Nour Eddine Es-Safi

Received: 24 August 2022 Accepted: 30 September 2022 Published: 9 October 2022

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**Copyright:** © 2022 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/).

as ingredients in ethnic food preparations and specialties, along with ethnomedicinal applications [3]. For example, a mixture of lichens called Yangben in the Rai and Limbu communities of East Nepal is mainly composed of *Ramalina* species [4]. Among these fruticose epiphytic species, *Ramalina conduplicans* Vain is common and one of the most widely-used edible lichen of the Ramalinaceae family, this is distributed in Central and Southeastern Asian countries [5].

In Southwestern China, people used to prepare their traditional cold dishes with this lichen at their marriage banquets [6], and it also has a long history of consumption as a spice in many places in India and as a traditional food by selected communities in East Nepal [7,8]. In addition to its useful edible properties, crude extracts from this lichen are used as ethnomedicine to counteract inflammation, anthelminthic [9], and act as an anti-diabetic [10], along with antibiotic activities [3,11,12]. Many studies on this lichen have focused on their nutritional value along with the important trace elements [13] and antioxidant properties of *R. conduplicans* [9,14] concerning sekikaic acid and homosekikaic acid [15]. However, systematic investigations of its constituents for their bioactive potentials have not been carried out to date.

Therefore, the antioxidant and alpha-glucosidase inhibiting properties of metabolites from *Ramalina conduplicans* were investigated here as part of our ongoing exploration of natural flora for the isolation of bioactive secondary metabolites [16,17]. Accordingly, we have designed a strategy and workflow based on the Total Ion Current Chromatography (TIC) of the acetone extract (AE) to recognize and to isolate compounds from *R. conduplicans* by UPLC-Q-ToF-MS/MS. AE and all the isolates were assayed for their antioxidant freeradical scavenging properties, including DNA damage protection and anti-hyperglycemic potential, through α-glucosidase inhibition.
