Herbal antibiotics beat drug-resistant pathogens

Several studies have demonstrated that if nothing was done urgently, most diseases will become untreatable with conventional antibiotics because of growing resistance of pathogenic organisms.

Indeed, owing to rising incidences of antimicrobial resistance against various chemotherapeutic and antimicrobial agents, the treatment of bacterial infections requires special consideration that may otherwise lead to grave prognosis.

Simultaneously, evolution of many a Multiple Drug Resistant (MDR) bacterial strains have further aggravated the present situation. In this scenario, scrutinizing for some alternative yet effective antibacterial therapeutics like herbs, nutritional immune-modulators, bacteriophages, avian egge antibodies and others have become inevitable.

Herbs have been a valuable source of medication in virtually all cultures and societies worldwide due to their important antimicrobial principles and phyto-constituents and wider therapeutic potentials.

Global usages of herbs as alternative and complementary medicines to various antimicrobials would lead not only to safeguard health issues and obtain optimum production from animals but will also ensure the public health issues including of food safety concerns viz., antibiotic residual effects in animal products (milk, meat) and zoonotic threats.

According to a recent study published in International Journal of Pharmacology, due to emerging drug resistant bacterial strains, nowadays many bacterial diseases do not respond to prescribed antibiotic treatments options and thus infectious diseases caused by various bacterial pathogens are flaring up and becoming uncontrollable.

The study is titled “Evidence Based Antibacterial Potentials of Medicinal Plants and Herbs Countering Bacterial Pathogens Especially in the Era of Emerging Drug Resistance: An Integrated Update.”

However, the study published in International Journal of Pharmacology and yet another one published in the journal Antibiotics have identified scientifically validated herbal antibiotics.

Allium cepa (Onions) and A. sativum (Garlic)
The ethanolic extracts from the cloves of A. sativum show antibacterial activity against MDR pathogens responsible for nosocomial infection. The ethanolic and aqueous extracts from the bulbs of A. cepa have been found to have antibacterial action against the common causes of urinary tract infections, Pseudomonas aeruginosa and Staphylococcus aureus, especially those isolated from high vaginal swabs.

Essential oils from garlic and other herbs kill Lyme disease bacteria
Oils from garlic and several other common herbs and medicinal plants show strong activity against the bacterium that causes Lyme disease, according to a study by researchers at Johns Hopkins Bloomberg School of Public Health. These oils may be especially useful in alleviating Lyme symptoms that persist despite standard antibiotic treatment, the study also suggests. The study, published October 16 in the journal Antibiotics, included lab-dish tests of 35 essential oils — oils that are pressed from plants or their fruits and contain the plant’s main fragrance, or “essence.” The Bloomberg School researchers found that 10 of these, including oils from garlic cloves, myrrh trees, thyme leaves, cinnamon bark, allspice berries and cumin seeds, showed strong killing activity against dormant and slow-growing “persister” forms of the Lyme disease bacterium.

Scent leaf/Holy Basil
Ocimum sanctum or Holy Basil: Ocimum is a household remedy throughout tropical and semitropical region of India and other Asian countries. Different parts of tulsi are traditionally utilized in the Ayurveda and Siddha systems of medicine for treatment of several aliments. The phytoconstituents of Ocimum sanctum is complex and include: Eugenol and urosolic acid; alkaloids and flavonoids; tannins and carbohydrates. The antibacterial activities of the plant is well proven against a wide variety of Gram positive and Gram negative bacteria including enteric organisms viz., E. coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella aerogens, Shigella dysentriae, Salmonella typhimurium, Vibrio cholera and Staphylococcus aureus. Equally are susceptible the fungi and viruses (including fish pathogens) indicating versatility of its anti-infective properties. Methanolic extracts and aqueous suspension of leaves and seeds oil of tulsi, all bear immune-modulatory properties. The leaves of the plant can induce cytokine secretion. The fixed oil and linolenic acid of tulsi possess good analgesic, antipyretic as well as anti-inflammatory activities.

Curcuma longa (Turmeric)
Curcuma longa, a perennial herb, is a member of the Zingiberaceae family. The roots form an important ingredient of Chinese and Ayurvedic systems of medicine. The rhizomes of C. longa possess a large inventory of moniterpenoids, sesquiterpenoids and curcuminoids, which show antibacterial, anti-inflammatory as well as antineoplastic activities. Curcuminoids, which are basically bioflavonoid compounds, exhibit a variety of beneficial therapeutic and preventive health effects.

Curcumin is the principal curcuminoid along with desmethoxycurcumin and bis-desmethoxycurcumin, the other two curcuminoids. Insecticidal activity of the turmeric rhizome has also been reported. Curcumin has antioxidant, anti-inflammatory, antiviral and antifungal actions. Curcumin blocks NF-κB and the motogenic response in H. pylori infected epithelial cells and carries thremendous therapeutic potential. It acts as an inhibitor for cyclooxygenase, 5-lipoxygenase and glutathione S-transferase. In addition to this, turmeric has been found to reduce the release of inflammation-inducing histamine, increase and prolongs the action of cortisol and improves circulation; thus increases the flushing toxins out of the body. Curcumin facilitates proliferation of CD4+ T-helper and B type immune cells.

Turmeric acts as a cholagogue, stimulating bile production, thus increases the digestion of fats and eliminating toxins from the liver. Wound healing and detoxifying properties of turmeric curcumin have also received considerable attention. The ethyl acetate extract of C. longa has demonstrated an excellent antibacterial activity against MRSA at a concentration of 0.125-2 mg mL-1. A study by Limtrakul et al. using RT-PCR showed that all three curcuminoids isolated from C. longa rhizomes inhibit expression of MDR-1 gene. The oleoresin (second fraction of the turmeric oil) contains ar-turmerone, turmerone and curlone and has been proven antibacterial against B. cereus, B. subtilis, B. coagulans, E. coli, S. aureus and P. aeruginosa.

Piper nigrum (Black pepper)
Both aqueous and ethanol extracts of black pepper inhibit the growth of penicillin G resistant strain of S. aureus. The extracts from Piper longum contain pharmacological molecules piperlonguminine, piperine and pellitorine, which exhibit significant antibacterial activity against Gram-positive bacteria and moderate activity against Gram-negative bacteria.

Piperine, [1-[5-[1,3-benzodioxol-5-yl]-1-oxo-2,4, pentadienyl piperidine, a pungent alkaloid present in P. nigrum, enhances the bioavailability of various structurally and therapeutically diverse drugs. Perhaps, it forms non-polar complexes with drug molecules and increases their permeability across the barriers. The Piper longum fruit extracts have also shown significant anti-mycobacterial activity against MDR Mycobacterium tuberculosis. Along with potent antimicrobial activity, black pepper is used to treat asthma, chronic indigestion, colon toxins, obesity, sinus congestion, fever, intermittent fever, cold extremities, colic, gastric ailments and diarrhea.

Syzgium aromaticum (Clove)
The aqueous and methanolic extract from whole clove is being efficiently used as an antimicrobial agent against food spoilage bacteria and food borne pathogens (S. aureus, P. aeruginosa, E. coli). The bread with a maximal of one per cent clove extract is acceptable for human consumption. Essential oils of clove possess antimicrobial properties against four Gram positive bacteria such as Brochothrix thermosphacta, Carnobacterium piscicola, Lactobacillus curvatus and Lactobacillus and Gram negative bacteria such as P. fluorescens and Serratia liquefaciens, E. coli, L. monocytogenes and S. enterica. Its antimicrobial properties are utilized in meat industry. A positive relationship has been established between the inhibitory effect of essential oils and the presence of eugenol and cinnamaldehyde. Crude methanolic extract inhibits gram-negative anaerobic pathogens, including Porphyromonas gingivalis and Prevotella intermedia. Eight pharmacologically active principles (5,7-dihydroxy-2-methylchromone 8-C-beta-D-glucopyranoside, biflorin, kaempferol, rhamnocitrin, myricetin, gallic acid, ellagic acid and oleanolic acid) have been identified following chromatographic fractionation of clove oil. The bioflavonoid, kaempferol and myricetin also show potent growth-inhibitory activity against the periodontal bacteria, Porphyromous gingivalis and P. intermedia. Clove and clove oils are used in day today’s life as potent anti-bacterial, anti-inflammatory and analgesic agents.

Thymus vulgaris (Thyme)
The oil of thyme is a naturally occurring antibacterial, anti-candidal and antioxidant agent when used topically due to which it is gaining popularity. Thyme has a broad antibacterial spectrum against both Gram positive and Gram-negative bacteria with a highly sensitivity against the former group. Thymol and carvacrol are active constituents of ethanolic extract of thyme. The essential oil of thyme has been found to have strong inhibition activity against S. sonnei, B. subtilis, L. monocytogenes S. enterica, C. jejuni and E. coli O157:H7.

The aqueous extract of thyme on the other hand was found to have significant inhibitory effects on the growth of H. pylori. Thymol decreases the viable count of S. typhimurium and S. sonnei in vitro. Carvacrol showed a dose-dependent inhibition of B. cereus. The MIC was as low as 0.03% (v/v) thyme oil against C. albicans and E. coli. The activity of thyme was modulated by alterations in pH and sodium chloride concentration of the medium.

The bacteriostatic and bactericidal properties of essential oil of thyme were evident against the non-toxigenic strain of E. coli O157:H7 in a broad temperature range. Lecithin weakened the antibacterial properties. Thyme showed greatest inhibitory potential against Aeromonas hydrophila compared to other psycrotrophic food-borne bacteria such as A. hydrophila, L. monocytogenes and Y. enterocolitica in in vitro conditions.

Zingiber officinale (Ginger)
Z. officinale possesses antimicrobial action against both Gram positive and Gram-negative microorganisms. It has potent anti-inflammatory, analgesic, antipyretic and antimicrobial activities. Methanolic extract of the dried powdered ginger rhizome contains 6-, 8-,10-gingerol and 6-shogoal which inhibited growth of different strains of Helicobacter pylori in vitro with a Minimum Inhibitory Concentration (MIC) of 6.25-50 μg mL-1.

Higher antibacterial efficacy has been shown by gingerols of the crude extract against H. pylori with an MIC range of 0.78-12.5 μg mL-1 showed significant activity against the CagA+ strains. Antibacterial activity has also been reported against the pathogens like S. aureus, S. pyogenes, S. pneumoniae and H. influenzae. The MIC and MBC values of various ginger extracts ranged from 0.0003-0.7 μg mL-1 and 0.135-2.04 μg mL-1, highlighting its therapeutic value.

Aloe vera
Aloe vera is obtained from the mucilaginous part of the centre of the leaf. Worldwide several studies have been suggested that Aloe vera, or Aloe vera gel has wide array of utility against various health-related disorders when applied orally and/or topically. The Aloe vera gel contains sugars, amino acids, vitamins A, B, C, E, enzymes, polysaccharides and minerals. Several reports have also shown encouraging role of Aloe vera in the management of both acute and chronic infected burn wounds.

B-sitosterol, acemannan and glycoprotein constituents of Aloe vera have therapeutic potentials. The antimicrobial potential of Aloe vera juice has been proved against a range of clinically relevant bacteria during in vitro studies. The various Gram-positive bacteria (Mycobacterium smegmatis, S. aureus, MRSA, Enterobacter cloacae, E. bovis, E. faecalis, Micrococcus luteus and Bacillus sphericus); Gram-negative bacteria (P. aeruginosa, K. pneumoniae, E. coli, Shigella flexneri and Salmonella typhimurium) and fungi (Candida albicans) were found susceptible to Aloe vera juice. Furthermore, Aloe vera extract has antimicrobial activity against M. smegmatis, E. faecalis, M. luteus and B. sphericus. Aloe vera juice can effectively be used in cosmetics and food industry as it has inhibitory effects against pathogenic bacteria causing food poisoning, especially the Gram-positive bacteria.

Azadirachta indica (Neem)
Neem leaves and oil possesses proven beneficial effects on several skin conditions and bacterial infections. The methanol extract from the leaves of Azadirachta indica has the highest antibacterial activity followed by the hexane, methanol, chloroform extracts from it. The water and hexane extracts from the seeds of A. indica inhibits the growth of Gram positive more strongly than Gram-negative bacteria.

Neem leaf extracts and oil have been demonstrated to posses wide antibacterial activity against various pathogens viz., E. coli, Pseudomonas aeruginosa, Aeromonas hydrophila, B. cerus, B. pumilus, S. aureus, S. typhi, K. pneumonae, Proteus sp., P. vulgaris, Vibrio sp., S. dysenterae, Enterococcus faecalis, Streptococcus sp. (S. mutans, S. mitis, S. sanguis, S. salivarius), M. tuberculosis and Yersinia enterocolitica.

Antibacterial potential of leaf extract of neem has been proven against methicillin-resistant S. aureus. The hexane extracts from the seeds produces larger zones of growth inhibition diameter, lower MIC and MBC values when compared to aqueous extracts. Moreover, it has been reported that the neem oil has low MIC against S. aureus, S. typhi, E. coli and P. aeruginosa. In vitro studies have also shown the antibacterial activity of neem oil and which indicated that 92% S. pyogenes, P. aeruginosa, Proteus sp. and E. coli are susceptibile to it.

Irodin A, recovered from leaves of neem, acts as a potent anti-malarial agent. The bark and oil of this plant have anti-tuberculosis (M. tuberculosis) and anti-leprotic properties. Neem oil show antiplaque actions while chewing its twigs help control dental tartar and caries. Recently, Kumar et al. indicated the utility of neem preparations for treating endometritis in cattle.

Tamarindus indicus (Black Tamarind tree/Icheku in Ibo)
Tamarind has been known as a medicinal plant due to its antimicrobial, antibacterial, antifungal and antiseptic properties. Tamarind leaves show broad spectrum of antimicrobial activity that can be attributed to its phyto-constituents like flavonoids, xyloglucan, benzyl benzoate, limonene, hexadecanol, pentadecanol and other polyphenols metabolites. These phytoconstituents have shown antibacterial and antifungal activities against B. subtilis, E. faecalis, S. aureus, E. coli, S. Typhimurium, P. aeruginosa and C. albicans.

Jatropha curcas (Lapalapa in Yoruba)
The ethanolic and methanolic extracts of Jatropha curcas possess broad-spectrum antibacterial activities. The extracts have lower potency for K. pneumoniae in comparison to other bacteria. The methanolic extract on the other hand showed significant antibacterial activity (MIC 0.5-10 mg mL-1) than the ethanolic extract (MIC 0.5-6.25 mg mL-1). This activity may be due to the presence of soluble phenolic and polyphenolic compounds.

Psidium guajava (Guava)
The antibacterial compound mainly found in guava is reducing sugar, alkaloids, saponins, tannins, phlobatannins, terpenoids and poly phenols. The crude aqueous and methanol extract from the leaf and bark of guava possess strong antibacterial activity against MDR Vibrio cholerae. The in vitro MIC for the crude aqueous and methanolic extract is 1,250 and 850 μg mL-1, respectively. These concentrations were bactericidal against 107 CFU mL-1 of V. cholera. The antimicrobial activity of guava has other advantage of being stable at 100°C for 15-20 min, indicating the non-protein nature of the active component (Rahim et al., 2010). The ethanol and hot water extracts possess less antibacterial activity compared to methanolic and ethyl acetate extracts.