**1. Introduction**

7

The global shrimp and prawn aquaculture industry is regularly threatened by outbreaks of microbial infections [1] that require antibiotics, antifungals, and antiviral agents participating in the selection of multidrug-resistant strains of microbes, pausing the grim scenario of the emergence of a "superbug" that could wipe out the global supply of penaeids [2]. In this context, there is an urgen<sup>t</sup> necessity to search for antimicrobial agents with original chemical frameworks, and such molecules could come from the flora of Asia and the Pacific, which is the oldest, largest, and richest on Earth, especially seashores, tidal rivers, and mangrove plants.

Mangroves are ecosystems of the tropical and subtropical seashores, estuaries, and tidal rivers characterized by a halophytic flora of mainly trees and shrubs divided into true mangrove or mangrove-associated species. True mangrove species are restricted to mangroves whereas mangrove-associated species are found along the seashores, and even inland. There are estimates of about 54 true mangrove plant species and 60 mangroveassociated species globally, which are home to shrimps, prawns, crabs, and fish [3]. Most mangrove species grow in Asia and the Pacific [4]. Examples of true mangrove plant species are *Excoecaria agallocha* L. (land zone), *Bruguiera gymnorhiza* (L.) Savigny, *Rhizophora stylosa* Griff. (intermediate zone), *Avicennia alba* Bl, and *Aegiceras corniculatum* (L.) Blanco

**Citation:** Sulaiman, M.; Nissapatorn, V.; Rahmatullah, M.; Paul, A.K.; Rajagopal, M.; Rusdi, N.A.; Seelan, J.S.S.; Suleiman, M.; Zakaria, Z.A.; Wiart, C. Antimicrobial Secondary Metabolites from the Mangrove Plants of Asia and the Pacific. *Mar. Drugs* **2022**, *20*, 643. https://doi.org/ 10.3390/md20100643

Academic Editors: Wenhan Lin, Guoqiang Li and Jing Xu

Received: 18 July 2022 Accepted: 26 September 2022 Published: 15 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/).

(fringing zone) [5]. Even though most of the global fish catches are directly or indirectly dependent on mangroves, these are on their way to extinction due to logging, agriculture, aquaculture, and urbanization, with an estimate of about 2–8% loss of surface per year [6]. Shrimps, prawns, and fish farming are the greatest threat to mangroves with, for example, approximately half of the 279,000 ha of mangroves in the Philippines lost from 1951 to 1988 [7]. Another aggravating factor is global warming, and consequently, a rise in sea levels that interfere with the growth of true mangrove plants.

Most plants in mangroves are Angiosperms organized phylogenetically into 11 major taxa or clades organized in three groups: (i) Basal Angiosperms: Protomagnoliids, Magnoliids, Monocots, Eudicots; (ii) Core Angiosperms: Core Eudicots, Rosids, Fabids, Malvids; and (iii) Upper Angiosperms: Asterids, Lamiids, and Campanulids. Within each clade, plants yield specific secondary metabolites to control and even communicate with phytopathogenic bacteria and fungi. Plants are challenged by phytopathogenic bacteria, fungi, and viruses and produce a vast array of antimicrobial secondary metabolites [8]. These antimicrobial principles fall into two main categories: phytoanticipins and phytoalexins. Phytoanticipins are antimicrobials present in plant tissues before pathogen challenges or inactive immediate precursors of phytoalexins [8].

Phytoanticipins and phytoalexins are mainly either phenolics, terpenes, or alkaloids with various levels of solubility in water and are extractable with water, polar organic (methanol, ethanol), mid-polar solvents (chloroform, dichloromethane, ethyl acetate), and non-polar solvents (hexane, petroleum ether) [9]. The measurement of the antibacterial and antifungal strength of extracts and secondary metabolites *in vitro* is quantitatively based on the minimum inhibiting concentration (MIC) and several thresholds of activity have been proposed [10]. Qualitatively, antibacterial and antifungal strength are appreciated by halos developed around a paper disc or an agar well expressed in the inhibition zone diameter (IZD) [10].

Colette et al. (2022) noted that the presence of *Atriplex jubata* S. Moore evoked some levels of remediation in the shrimp farms of New Caledonia [11] and this review aims to attempt to answer the following points: What is the current knowledge on the distribution of antibacterial, antifungal, and antiviral principles from the mangrove plants of Asia and the Pacific? What are the strongest antimicrobial principles isolated thus far from these plants? What is the spectrum of activity of the antimicrobial principles? What are the medicinal values of these plants? What is the potential usefulness of these plants as remediation of shrimp farming? We hypothesize that a shrimp or prawn farming system preserving healthy mangroves could be a mean to solve the increasing problem of infection.

#### **2. Distribution of Antibacterial, Antifungal, and Antiviral Principles Various Mangrove Plants**

The enumeration of mangrove and mangrove-associated plants is provided in Table S1, and the chemical structures of the antimicrobial secondary metabolites identified from these plants is given Figure S1.
