Extracts of Sida cordifolia contain polysaccharides possessing immunomodulatory activity and rosmarinic acid compounds with antibacterial activity

Abstract

Background The overuse of antibiotics has led to increased antimicrobial resistance, but plant-derived biological response modifiers represent a potential alternative to these drugs. This investigation examined the immunomodulatory and antibacterial activities of Sida cordifolia (used in ethnomedicinal systems to treat infectious disease). Methods Successive extractions were performed from the roots of these plants in hexane, chloroform, methanol and water. Immunomodulatory activity was determined in a series of experiments measuring the responses of splenocytes, macrophages and an in vivo model of innate immunity (Galleria mellonella). Antibacterial activity was assessed by determining minimum inhibitory/bactericidal concentrations (MIC/MBCs) for various Gram-positive and Gram-negative bacterial strains. Results Immunomodulatory activity was confined to the aqueous extract, and further fractionation and biochemical analysis yielded a highly potent polysaccharide-enriched fraction (SCAF5). SCAF5 is a complex mixture of different polysaccharides with multiple immunomodulatory effects including immune cell proliferation, antibody secretion, phagocytosis, nitric oxide production, and increased expression of pro-inflammatory cytokines. Furthermore, Galleria mellonella pre-treated with SCAF5 produced more haemocytes and were more resistant (P < 0.001) to infection with methicillin-resistant Staphylococcus aureus (MRSA) with a 98% reduction in bacterial load in pre-treated larvae compared to the negative control. The antibacterial activity of Sida cordifolia was confined to the methanolic fraction. Extensive fractionation identified two compounds, rosmarinic acid and its 4-O-β-d-glucoside derivative, which had potent activity against Gram-positive antibiotic-resistant bacteria, including MRSA. Conclusions Sida cordifolia counters bacterial infections through a dual mechanism, and immunomodulatory polysaccharides from this plant should be isolated and characterised to realise their potential as anti-infective agents. Such properties could be developed as an antibiotic alternative (1) in the clinic and (2) alternative growth promoter for the agri-food industry.

Cytotoxicity and Identification of Antibacterial Compounds from Baillonella toxisperma Bark Using a LC-MS/MS and Molecular Networking Approach

“…Indeed, previous studies on the plant have shown that polyphenols, tannin and flavonoids are responsible for its antibacterial activities [ 9 ]. Several other studies have shown strong antimicrobial activities of rosmarinic acid mainly present in the F2 fraction of B. toxisperma [ 42 , 43 , 44 , 45 ]. Similarly, several studies have shown antibacterial and antioxidant activities of quercetin and its derivatives [ 46 , 47 , 48 ].…”

Galleria mellonella as a Novel In Vivo Model to Screen Natural Product-Derived Modulators of Innate Immunity

“…2022, 12, x FOR PEER REVIEW G. mellonella are superior to other invertebrate models due to their larger size facilitating experimental manipulation (e.g., drug administration) and the ability to grow at a wide range of temperatures (20-37 °C). In addition, they confer several key advantages over small animal models due to their short data generation time (24-48 h versus weeks), being relatively inexpensive, being not constrained by stringent ethical requirements, and in many cases, producing comparable data to animal studies [24][25][26]. Recently, its genome was fully sequenced, opening opportunities for genetic and epigenetic studies [27].…”

“…A review of the G. mellonella non-vertebrate immune system components (e.g., melanisation, nodulation and encapsulation) [21,34], its use in toxicology studies [23] and an in-depth comparison to the mammalian immune system [33,35] is beyond the scope of G. mellonella are superior to other invertebrate models due to their larger size tating experimental manipulation (e.g., drug administration) and the ability to grow wide range of temperatures (20-37 °C). In addition, they confer several key advan over small animal models due to their short data generation time (24-48 h versus w being relatively inexpensive, being not constrained by stringent ethical requirement in many cases, producing comparable data to animal studies [24][25][26]. Recently, its ge was fully sequenced, opening opportunities for genetic and epigenetic studies [27].…”

Sida cordifolia - an Update on Its Traditional Use, Phytochemistry, and Pharmacological Importance

“…There is a substantial antibacterial activity of the phytocompounds against gram-positive bacteria (MIC values range from 0.5 to 2.0 mg/ml), in particular against methicillin-resistant Staphylococcus aureus (MRSA). Rosamarinic acid 4-O-β-d-glucoside (100 μM; 99.9%) significantly lowers the MRSA in vivo microbial load in MRSA infected Galleria larvae [40].…”