Antimicrobial Potential of Curcumin

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1		Marco Dacrema	+ 1992 word(s)	1992	2022-03-11 08:45:39	\|
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This entry is adapted from the peer-reviewed paper 10.3390/antibiotics11030322

Curcumin is a bioactive compound that is extracted from Curcuma longa and that is known for its antimicrobial properties. Curcuminoids are the main constituents of curcumin that exhibit antioxidant properties. It has a broad spectrum of antibacterial actions against a wide range of bacteria, even those resistant to antibiotics. Curcumin has been shown to be effective against the microorganisms that are responsible for surgical infections and implant-related bone infections, primarily Staphylococcus aureus and Escherichia coli. The efficacy of curcumin against Helicobacter pylori and Mycobacterium tuberculosis, alone or in combination with other classic antibiotics, is one of its most promising antibacterial effects. Curcumin is known to have antifungal action against numerous fungi that are responsible for a variety of infections, including dermatophytosis. Candidemia and candidiasis caused by Candida species have also been reported to be treated using curcumin. Life-threatening diseases and infections caused by viruses can be counteracted by curcumin, recognizing its antiviral potential.

curcumin antimicrobial potential

1. Introduction

Curcumin is a bioactive curcuminoid polyphenol that is isolated from the rhizomes of Curcuma longa. Chemically, curcumin is 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione. It is also termed as diferuloyl methane ^[1]. Curcuma longa is commonly known as turmeric, which belongs to the Zingiberaceae family. Turmeric is found abundantly and naturally in tropical areas, on the Indian subcontinent, and in South Asia. Turmeric is dark yellow in color due to the presence of a wide variety of polyphenolic curcuminoids. Curcuminoids such as curcumin, bisdemethoxycurcumin, and dimethoxy-curcumin are found in Curcuma longa ^[2].

Turmeric has been used in the Ayurvedic medicine system for the management of various medical disorders such as jaundice, skin infections, wounds healing, flatulence, sprains, arthritis, and stomach disturbances since ancient times. Curcumin has also been established as an anti-asthmatic, antiarthritic, anti-inflammatory, antioxidant, antimicrobial, cardio-protective, and immuno-modulatory agent ^[3]. Curcumin targets several signaling molecules while illustrating cellular activity, supporting its numerous health benefits. Curcumin supplements have been found to have potential nephroprotective, analgesic effects and to be useful in the management of metabolic syndromes because of its antioxidant effects ^[4]^[5].

Although curcumin has a broad spectrum of pharmacological properties, a critical challenge towards desirable therapeutic applications is its poor bioavailability, which is due to its poor intestinal absorption, hydrophobic character, and rapid metabolism. Its systemic bioavailability is very low after oral administration. However, studies have found that a small amount of systemically available curcumin has a marked therapeutic effect. Different agents were analyzed to better determine the bioavailability of curcumin ^[6]. Curcumin is considered as a potential agent for the development of novel natural products, including nanocrystals and micro-particles, to improve its stability versus the identified factors, and to manipulate bioactivities ^[7]^[8]. The antimicrobial mechanistic pathway of curcumin usually includes interference from fundamental cellular division and the induction of the protein-filamenting temperature-sensitive mutant Z (FtsZ). The cytoskeleton of bacteria is essential for development and cell division, whereas the FtsZ protein is associated with microbial cell replication and is the first protein that emerges at the imminent division site ^[9]^[10].

2. Antibacterial Effect

Curcumin inhibits the growth of both Gram-negative and Gram-positive bacteria. ^[11]^[12]. Different antimicrobial strains such as Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and Staphylococcus aureus were assayed. They reported that curcumin showed potential antibacterial activity against all of the tested species, indium diacetyl-curcumin revealed an antibacterial effect against Staphylococcus epidermidis and Staphylococcus aureus, diacetyl-curcumin had no antibacterial effect on any species, whereas it was reported that indium curcumin demonstrated significant antibacterial potential against all of the tested strains. They also determined the MIC of all of the compounds against each of the antibacterial species and found that the MIC of curcumin against Staphylococcus aureus and Staphylococcus epidermidis was 187.5 µg/mL and 46.9 µg/mL, respectively. The MIC for indium curcumin was determined to be slightly less than that of the other two species above, which were 93.8 µg/mL and 23.4 µg/mL, respectively. Thus, their analysis established that indium curcumin has a higher antibacterial effect compared to curcumin ^[13].

A lot of in vitro investigations have shown that curcumin possesses antimicrobial activity towards microbes such as and Gram-positive and Gram-negative bacteria ^[14]^[15]^[16]^[17]. Curcumin has a wide range of mechanistic pathways that are responsible for these antimicrobial actions. These pathways may include DNA replication inhibition, the modifications in plasmid gene expression, cell membrane deterioration, and motility reductions.

Curcumin has been reported to be a promising breaker of antimicrobial resistance, as curcumin has the potential to restore the effectiveness of failed antimicrobials by lowering their MICs. Researchers investigated the resistance of a multi-drug resistant strain of Mycobacterium abscessus (isolated from a 66-year-old tuberculosis patient) against curcumin. In 2018, Marini treated resistant strains of M. abscessus with a combination therapy with different concentration of curcumin with clarithromycin, linezolid, ciprofloxacin, and amikacin. Curcumin slightly decreased the pathogenicity (degree or state of being pathogenic) at 1/8 × MIC, while at 4 × MIC, it totally blocked biofilms from 4 to 8 days. Additive curcumin and amikacin therapy caused a significant decline in the viable cell count as well as a decrease in the microbial colonies. While curcumin was the main agent, the most notable feature observed was the biofilm destruction on the 4th and 8th days. These results backed up past evidence that curcumin can help break resistance to antibiotics. Curcumin, alone or in combination with antibiotics, may help to establish a new approach for combating the pathogenicity and drug resistance of M. abscessus ^[18]. Methicillin-resistant Staphylococcus aureus-related hospital infections are a global public health issue. In combination with other antibiotics, curcumin is effective against such resistance. Due to its low systemic bioavailability, curcumin was formulated in the form of graphene oxide nanoparticles and was targeted for antibiotic activity. The fabricated curcumin nanoparticles showed low toxicity and effective anti-bacterial activity against antibiotic-resistant infection at concentrations of less than 2 µg/mL ^[19].

3. Antifungal Effect

Curcumin was quite effective against isolated strains of Paracoccidioides brasiliensis, but it had no effect on Aspergillus strains. The adherence of Candida species was more efficiently inhibited by curcumin compared to fluconazole, especially in the buccal mucosal strains that were isolated from patient suffering from AIDS, proving that curcumin is indeed a potential natural compound that deserves more research into its pharmacological activity in immunosuppressed individuals. Thus, the researchers concluded that curcumin is an effective antifungal agent for the management of P. brasiliensis infection compared to fluconazole ^[20].

A graphical presentation of the antimicrobial effect of curcumin is provided in Figure 1.

Figure 1. Anti-microbial spectrum of curcumin.

4. Antiviral Effect

Curcumin appears to be a potent antiviral agent against various viruses, including feline infectious peritonitis virus, respiratory syncytial virus (RSV), para influenza virus type 3, herpes simplex virus (HSV), vesicular stomatitis virus, and flock house virus, as well as others ^[21]. Combating viral diseases, particularly those triggered by evolving viruses, have always been a dilemma. Curcumin’s antiviral properties emerge from its potential to modulate a variety of the molecular targets that are involved in cellular events such as transcription regulation and the activation of cellular signaling pathways such as the apoptosis and inflammation pathways through intermolecular interaction ^[22]. The mechanism and events adopted by curcumin to initiate antiviral activity are shown in Figure 2.

Figure 2. Antiviral mechanism of curcumin in the host cell. Chemotherapeutic action is attracted to certain crucial stages in the viral life cycle. These steps include the attachment of the virion to its cellular receptor, its consecutive entry, followed by the viral genome transcription and replication step, and then its translation, virion assembly, and finally release. Curcumin inhibits the action of viral envelope proteins, preventing viral attachment and entry. In addition, certain signaling pathways, inflammation, and translation/transcription machineries are modulated by curcumin that then becomes block viral replication. Apart from this, curcumin disrupts the integrity of the viral envelope and thus acts as a virucidal agent. A few of the viruses against which curcumin has shown a versatile antiviral effect are shown in the circles.

Viruses grow on the surface of cell membrane through attachment—this is considered as the initial event. According to a recent study, infections that are induced by arthropod-borne viruses such as Chikungunya and Zika are able to be prevented by curcumin by preventing the virus from attaching to the cell surface ^[23]. Curcumin enhanced lipid raft development in Madin–Derby bovine kidney (MDBK) cells, affecting the entry stage of bovine herpes virus type 1, reducing their total viral yield in a dose-dependent manner ^[24]. Curcumin has shown its antiviral effects against Zika virus (ZIKV) by preventing cell attachment. Only the cells that had been treated before or after infection decreased Zika virus recovery in multiple time-of-addition assays, meaning that curcumin predominantly works against ZIKV at cell entry/attachment and not during later stages of infection ^[23].

5. Synergistic Effects

In combination therapy, natural products offer their purported medicinal effects. In contrast, using nanoparticles as therapeutic agents for oral use can help to overcome certain drawbacks and to provide benefits over selective chemotherapy in the form of low toxicity and the stimulation of antibiotic resistance ^[25]. However, combination therapy also helps to overcome some of the associated barriers. In this regard, curcumin and quercetin were co-delivered to evaluate its antibacterial potential. The results suggested that the co-delivery of curcumin and quercetin showed antimicrobial activity against MRSA at lower concentrations compared to their individual administration, and the resultant effect was in the form of synergy ^[26]. Bacterial growth can also be controlled using a new approach—photodynamic inactivation. Staphylococcus aureus growth was inhibited by the combination therapy of curcumin and hypocrellin B, where the photodynamic efficacy of hypocrellin B was potentiated by curcumin ^[27].

Combination therapies can also be used to overcome the resistance crisis. When hybridized with octa-arginine—a cell penetrating peptide, curcumin showed good antibacterial action. The result was in a synergic form with a bactericidal effect and occurred through curcumin targeting the bacterial cell membrane ^[28]. Similarly, another small peptide—bacteriocins—has demonstrated efficient anti-bacterial activity; however, due to resistance, it does not provide the desired therapeutic output. Curcumin was co-administered with bacteriocins against Staphylococcus epidermidis and E. coli. Curcumin potentiated the antibacterial activity of bacteriocins, showing that it can be used in biomedical applications in combination with curcumin ^[29]. Curcumin was also co-delivered with suberoylanilide hydroxamic acid in order to improve its water solubility and efficacy. The results showed that such a synergistic combination displayed stronger antibacterial action for curcumin than suberoylanilide hydroxamic acid and pure curcumin alone ^[30].

Drug-resistant strains of Staphylococcus aureus are to the cause of infection-related mortality. Many antibiotics have been rendered inactive due to the advent of drug resistance. Recurrent latent infections are caused by the low penetration and retention of antibiotics in mammalian cells. Individually, curcumin and berberine were shown to be less effective due to low penetration and hydrophobicity. The co-delivery of both once again showed no remarkable antimicrobial synergistic effect. However, the loading of both into liposomes displayed a significant synergistic effect against MRSA ^[31]. Similarly, curcumin in combination with xylitol was evaluated for its antibacterial and antifungal activities. The combination effect was in the form of synergistic effect against Staphylococcus aureus, P. aeruginosa, and C. albicans ^[32]. A recent in vitro study showed that the combination of curcumin and polymyxin-B displayed a synergistic effect against Gram-positive and Gram-negative bacteria ^[33].

6. Therapeutic Challenges and Solutions

Due to its low side effects and wide range of conventional applications, curcumin has been used in several antimicrobial studies. The intrinsic physicochemical characteristics of curcumin derivatives, such as their low bioavailability, hydrophobic nature, photo-degradation, rapid metabolism, chemical instability, and short half-life, are the major challenges that restrict their pharmaceutical impact despite their wide spectrum of results ^[34]. Novel strategies have recently been implemented to attempt to resolve these limitations and to boost the therapeutic ability of curcumin. These problems are being overcome by integrating curcumin in nanoformulations. Using different methods to integrate curcumin into nanocarriers is a fruitful and effective alternative for increasing curcumin’s biological function that also improves its solubility, bioavailability, long-term circulation, and retention in the body as well as overcomes curcumin’s physiological barriers. As such, nanocurcumin fabrication is a major tool and solution to the posed therapeutic challenges that are in the way of curcumin delivery.

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