Jatropha Curcas: A Botanical Ally in the Fight Against Antibiotic-Resistant Bacteria
Table of Contents
Introduction
The rise of antibiotic-resistant “superbugs” poses a critical threat to global health, rendering many of our most effective medicines obsolete. As conventional drug discovery pipelines struggle to keep pace, scientists are turning to an ancient source of healing: the natural world.
Plants, in particular, have evolved complex chemical defenses over millennia, creating a vast library of compounds with potent medicinal properties. This excerpt from a doctoral thesis explores the potential of one such plant, Jatropha curcas.
The following discussion, taken directly from the research, delves into how extracts from its seeds could be combined with existing antibiotics to create powerful new therapies, potentially revitalizing our arsenal against some of the most dangerous clinical bacterial strains.
Excerpt
“J. curcas has traditionally been used in medicine and its biological properties extensively investigated. During the last few decades, numerous biologically and medicinally important phytochemicals including flavonoids, tannins, steroids, saponins, glycosides, cardiac glycosides, volatile oils have been reported in J. curcas seed, increasing its medicinal importance.
Some of the bioactive constituents of this plant have been used to cure various diseases such as coated tongue, dysentery, infertility, gonorrhea, hemorrhoids, skin infections and inflammation. Moreover, the phytochemicals play vital roles in plant defense mechanism against different microbial infections.
The current study aims to develop a novel strategy towards the discovery of new antibiotics by combining J. curcas seed oil and de-oiled seed extracts with commercially available antibiotics against various clinical, MRSA and MDR bacterial strains to combat prevailing antibiotic resistance.
The study included FTIR spectroscopic analyses of J. curcas seed oil and methanolic, n-hexane and aqueous extracts of its de-oiled seed. Various absorption bands in the FTIR spectra indicated the presence of different biological compounds such as proteins, carbohydrates, lignin, aromatic compounds, alkaloids, esters (phorbol esters and fatty acids methyl esters), amides, cellulose, hemicellulose and fatty acids.
Alkaloids, phorbol esters, fatty acids and its methyl esters might be the main antimicrobial components as their antimicrobial activity has been reported earlier.
The GC-MS analyses determined the presence of a broad range of bioactive compounds in J. curcas extracts. In seed oil and n-hexane extract, a number of long chain fatty acids were detected.
The antibacterial mechanism of long chain fatty acids is still unknown but the OH groups present in these fatty acids target the bacterial cell membrane. Due to their amphipathic nature, fatty acids can solubilize various membrane components such as lipid bilayer and proteins that may lead to cell lysis.
They also affect various cellular processes including electron transport chain, oxidative phosphorylation reaction, enzyme inhibition, production of peroxides and altering electron gradient resulting in the leakage of cellular components from cells and manifests various inhibitory and bactericidal effects.
In the present study, beta-monolaurin (ester of glycerol and lauric acid) and 9-hexadecenal and 1-docosanol, found in the methanolic extract of J. curcas de-oiled seed, has previously been reported to have antimicrobial potential that may damage extracellular membrane, denature proteins and DNA or inhibit various macromolecular biosynthesis processes.
Another medicinally important compound, I-(+)-Ascorbic acid 2,6-dihexadecanoate, identified in the methanolic extract has strong antioxidant activities and has been used in wound healing. In GC-MS analysis of aqueous extract, a number of bioactive compounds such as 1,4-dithiane, dodecanoic acid, methyl ester, methyl tetradecanoate, vitamin D3, palmitic acid, methyl ester, isopropyl linoleate and di-n-octyl phthalate were identified.
The antimicrobial potential of the aqueous extract can be attributed to the presence of these compounds. Vitamin D3, identified in aqueous extract, which has the capability to mediate innate immunity in humans and can be used as defense against various infections.
In the present study, methanolic extracts among others was found comparatively more potent against clinical, MDR and ATCC bacterial strains. Individually, methanolic extract exhibited the highest activity against S. aureus, S. aureus ATCC and MRSA4 among the clinical isolates, reference or MDR strains, respectively. Methanolic extracts of a number of medicinal plants had previously been reported with higher antimicrobial potential compared to n-hexane and aqueous extracts, suggesting its higher biological significance.
This study also affirmed the antimicrobial potency of methanolic extract by molecular docking studies that unveiled beta-monolaurin as the best conformation in the active pocket of potential antimicrobial MurF target. Similarly, 9,12 octadecadienoic acid present in n-hexane extract also showed strong interaction and affinity with MurF ligase active pocket.
In contrast to the previously reported data, methanolic extract exhibited greater activity against Gram negative than Gram positive clinical isolates. However, some studies revealed that Gram positive strains were less susceptible to bioactive compounds than Gram negative ones because the outer membrane of the latter is not fully impermeable.
In contrast, in case of MDR strains, the extracts and oil were more active against Gram positive than Gram negative bacteria, probably due to the impermeability of outer membrane of the latter.
The selected antibiotics at initial concentration were found active against most of the clinical and MDR bacterial strains in the following order: moxifloxacin > ciprofloxacin > ofloxacin > cefotaxime > rifampicin.
Combinatorial therapy or synergistic interaction is recommended as an effective strategy to help resolve the issue of antibiotic resistance, cellular toxicity and long-term treatments of the available antibiotics. It can also add to find broad-spectrum antibiotics compared to monotherapies.
In the current study, antibiotics were combined with potent bioactive compounds of the J. curcas, aiming to increase their antibacterial potential, overcome resistance and reduce the cost and duration of antimicrobial therapy. When evaluated in combination with J. curcas extracts or seed oil, the activity of the selected antibiotics increased (MICs range of 0.097 to 100 mg/mL) as compared to the activity of J. curcas extracts or seed oil when screened alone (MIC range of 50 to 200 mg/mL).
The antibiotic/extracts combinations screened as antibacterial agents in this study, were also studied to evaluate their synergistic, indifferent, additive or antagonistic effect that occurs when the antibacterial activity of the drug combination exceeds the sum of the individual drug activities, the activity of both drugs (in combination or individually) remains equal, there is no obvious change in the activity of both drugs (in combination or individually) or the activity of one drug is reduced in the presence of other, respectively.
In combinations, methanolic extract and rifampicin exhibited synergistic rates of 15.29% against selected pathogenic strains. These treatments exhibited the highest synergistic activities against A. baumannii, E. coli, E. faecalis, S. aureus, and P. aeruginosa, methicillin resistant S. aureus (MRSA2, MRSA3, MRSA4 and MRSA5), A. baumannii (MDR strain), P. chlororaphis, E. coli ATCC25922 and S. aureus ATCC25923. Earlier studies have reported strong synergism between rifampicin and other antimicrobial agents.
This makes rifampicin a strong candidate for combination antimicrobial therapies.
In view of the previous combination therapy studies, it is held that phytochemicals from J. curcas seed oil and de-oiled seed extracts combined with some antibiotics can make human pathogenic clinical bacterial and MDR strains more sensitive. Purification of these phytochemicals and their utilization in combination with commercially available antibiotics against pathogenic bacteria in nosocomial and other infections could prove to be the next step in the discovery of new antibiotics to combat antibiotic resistance in bacteria.
The combination of antimicrobial compounds showing in vitro synergistic activities against infectious agents are considered as ideal options for effective treatment of bacterial infections, especially in patients with hardly curable infections. Since the discovery and development of new classes of potent antibiotics is the need of the day, the crude extracts and seed oil of J. curcas appear to be promising as these exhibited potent antibacterial activities against varied clinical pathogenic and multidrug resistant bacterial strains.
Among all de-oiled seed cake extracts and seed oil of J. curcas, crude methanolic extracts exhibited comparatively more potent antibacterial activities both individually and in combination with selected commercial antibiotics.”
Source Citation
Researcher’s full name: Abdul Haq
Title: Biotechnological Applications of Jatropha curcas Seeds for Bioenergy Carriers and Bioactive Compounds
Guide(s): Dr. Malik Badshah
University: Quaid-i-Azam University, Islamabad
Completed Date: 2020
Exit page number: Pages 73-78
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