2.4.11. Clade Campanulids

The ethanol extract of the roots of *Pluchea indica* (L.) Less. (Asteraceae) repressed *E. coli*, *B. cereus*, *Pseudomonas fluorescens*, *S. aureus*, and *S. typhimurium* [258]. The aqueous extract of leaves inhibited HIV-1 [259]. The aqueous extract of berries of *Scaevola taccada* (Gaertn.) Roxb. (Goodeniaceae) restrained HIV-1 [259]. The methanol extract of leaves (500 μg/well) evoked halos with *V. cholerae*, *K. pneumoniae*, *S. typhi*, *S. sonnei*, *F. oxysporum*, *Fusarium solani*, *Rhizoctonia solani*, and *Odium monilioides* [260]. This coastal shrub yields the strong antifungal furanocoumarin scataccanol (**87**) as well as 4-formylsyringol (**88**) (Table S2) [261].

#### **3. Antimicrobial Extracts and Compounds from Mangrove and Mangrove-Associated Plants with the Potential to Be Used for Shrimp Farming**

According to Kuete (2010), crude extracts with MIC values less than 100 μg/mL are antimicrobial [10]. Here, we define a very strongly active extract with a MIC value below 10 μg/mL. An isolated compound is defined as very strongly active for a MIC value below or equal to 1 μg/mL (as well as less than 1 μg/thin layer chromatography), strongly antibacterial (or antifungal) for a MIC value above 1 μg/mL and equal to or below 50 μg/mL, moderately antibacterial (or antifungal) for a MIC from 50 and below 100 μg/mL, weakly antibacterial (or antifungal) for a MIC from 100 and below 500 μg/mL, very weakly antibacterial (or antifungal) for a MIC ranging from 500 to below 2500 μg/mL, and inactive for a MIC value above 2500 μg/mL.

For antiviral principles, we sugges<sup>t</sup> that a compound with an IC50 value below or equal to 1 μg/mL is very strongly active, for an IC50 value above 1 and equal to or below 20 μg/mL strongly antiviral, for an IC50 above 20 and below or equal to 100 μg/mL moderately antiviral, for an IC50 above 100 and below or equal to 500 μg/mL weakly antiviral, for an IC50 ranging from above 500 to below or equal to 2500 μg/mL very weakly antiviral, and inactive with an IC50 value above 2500 μg/mL.

Using these criteria, the strongest antimicrobial extracts from mangrove and mangroveassociated plants that could be of value for shrimp farming are from *C. inophyllum* (*S. aureus*, *T. rubrum*) [63], *T. catappa* (*E. faecalis*) [129]., *C. manghas* (*E. coli*, *P. aeruginosa*, VSV) [17,220], and *C. odollam* (HSV) [223].

The strongest antimicrobial principles identified from the mangrove and mangroveassociated plants that could be of value for shrimp farming are as follows (Figure 1):

(i) Antibacterial: Lupinifolin (**35**) (Gram-positive and Gram-negative) [116]; 7-hydroxycadalene (**46)** [152].

(ii) Antifungal: Lupinifolin (**35**) (Yeasts) [116].

(iii) Antiviral: Naringenin (**9**) [50], verbascoside (**81**) [248], inophyllum B (**15**) [61], 12- deoxyphorbol 13-(3*E*,5*E*-decadienoate) (**18**) [69], 5*β*-carboxymethyl-3*α*-hydroxy-2*β*-hydroxymethyl-1- methylpyrrolidine (**19**) [70], deguelin *(***33***)* [117], deoxypodophyllotoxin (**3**) [25,116] (9*R*,10*R*, 23*R*)-21,23:23,27-diepoxycycloarta-1,24-diene-3,27-dione (**49**) [156], gallic acid (**21**) [83], and 4,5-di-*O*-caffeoylquinic acid (**69**).

(iv) We note that most of these principles are hydrophilic or amphiphilic (Figure 1).

**Figure 1.** Natural products from mangrove plants with very strong antimicrobial activities.

#### **4. Spectrum of Activity of Antimicrobial Extracts and Principles from Mangrove and Mangrove-Associated Plants**

The following observations can be made:


#### **5. Medicinal Use of Mangrove and Mangrove-Associated Plants**

One could sugges<sup>t</sup> the use of medicinal plants as a more sustainable alternative to chemotherapy in paenid aquaculture. Therefore, the possible beneficial effect of mangrove and mangrove-associated plants for the sanitation of shrimp farms is reinforced by the observation that 85 plants were used for the treatment of infectious diseases including mainly diarrhea, dysentery, and wounds [264–294] (Table S1). The pharmacological effect of these plants involves active principles that are potentially able to act on paenids, which could be examined further.

#### **6. Mangrove and Mangrove-Associate Plants as Remediation of Shrimp Farming?**

Shrimp and prawn farms are regularly affected by (+)-RNA viruses such as the Taura syndrome virus, Yellow head virus, and Gill-associated virus as well as DNA viruses (WSSV, Monodon Baculovirus) and Gram-negative bacteria such as *Hepatobacterium penaei* and *Vibrio* spp. [295]. Synthetic drugs are being used in an attempt to evade economic losses but threaten the environment and contribute to the selection of multidrug-resistant pathogenic microorganisms. Being able to produce antimicrobial principles (some of them water soluble like ellagic acid), mangrove and mangrove-associated plants could be used as a source of natural agents and/or afford ecological systems to combat the infections with shrimps and prawns. Polar organic and aqueous extracts of most mangrove and mangrove-associated plants exhibit broad-spectrum antibacterial, antifungal, or antiviral properties in vitro, suggesting that antimicrobial secondary metabolites from plants and plant litter in the sea and brackish waters could afford some control against the overgrowth of pathogenic microbes. Of note, *P. pinnata* ethanol extract of leaves given to Penaeus monodon as part of feed at the dose of 300 μg/g of body weight/day evoked some levels of protection against WSSV [262]. Gallic acid (**21**), which abounds notably in the true mangrove trees *R. apiculata* and *A. corniculatum* is strongly antiviral and protected shrimps against WSSV [84]. Gallic acid (**21**) may, at least in part, account for the fact the aqueous extract of the true mangrove tree *C. tagal* given at the dose of 10% of the body weight, twice a day, protected shrimps against WSSV [263]. Furthermore, gallic acid (**21**) decreases microbial proliferation in mangrove soil [296] as well as the growth of microalgae [297], which contribute to a decreased production in shrimp aquaculture [298], at least in part, to the alteration in the shrimp's immune system [299]. The control of pathogenic bacteria may have some beneficial effects for the symbiotic bacteria of shrimp against pathogenic microorganisms [300]. Furthermore, phenolic acids from mangrove and mangrove-associated plants could, by chelation, protect shrimps against toxic metals including cadmium [301,302]. Therefore, it is possible to extend the protective effect of mangrove and mangrove-associated plants to fisheries and crab farming, the latter being affected by *Vibrio* species [165]. Another interesting feature of mangrove plants is that they are a host for microorganisms for Actinomyces producing antibacterial principles [303].
