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Authored By Pharmaceutical Scientist Dr. Harmeet Kaur, PhD
The walnut genus (Juglans) belongs to the Juglandaceae family of plants, generally characterized by large, aromatic leaves, and catkin flowers. This family has about 10 genera' and approximately 50 species. Some important members of the walnut family are Juglans nigra (Black Walnut), Juglans regia (Persian walnut/English walnut), and Juglans cinerea (Butternut). For thousands of years, the black walnut has been used in herbal medicine.
The black walnut tree produces a globular fruit that contains a grooved nut in its yellowish-green hull (also called fruit wall or husk). Due to chemical oxidation, it turns usually dark brown to black. Romans and Greeks called the black walnut fruit the "imperial nut" and used the hull to treat intestinal diseases.
The hull has also been used for the treatment of snakebites, open wounds, scurvy, ulcers, and as one of the most effective laxatives available. The outer hull has also been used as a part of hair dye due to its dark color until the early 1900s.
It is a good source of beta-carotene, plant acids, tannins, omega-fatty acids flavonoids, minerals, B-vitamins, and vitamin C. Recently, the walnut hull has received exaggerated interest in modern medicine owing to its excellent antioxidant activities since it is a waste product that has been extensively used in traditional medicine for the alleviation of pain and treatment of skin diseases [1,2].
Black walnut hull contains several active ingredients, of which the most important are juglone (5-hydroxy-1,4-naphthoquinone), tannins (most common hydrolyzable tannins such as ellagic acid and tannic acid), and iodine. Juglone is a brown constituent of the black walnut hull, bark, leaves, and even roots. In living plant tissues, juglone exists in bound form (juglone glucoside) or reduced form (hydrojuglone) which are non-toxic forms but on releasing in the environment in these nontoxic forms, it is hydrolyzed or oxidized to the toxic form, juglone (Fig 1).
It is an allelochemical with phytotoxicity. The allelochemical means that the plant produces this chemical to keep other plants from growing around it. Subsequently, fungus and yeast in humans are also plants, it has been speculated that it will also exhibit anti-fungal potential.
Black walnut hull is also a source of organic acids, flavonoids, glycosides, terpenes, antioxidants such as the polyphenols and γ-tocopherol, higher levels of monounsaturated fatty acids, coumarins, and essential oils,. The specific compounds identified included gallic, caffeic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, quercetin-3-rutinoside, quercetin-3-galactoside, quercetin-3-pentoside, quercetin-3-arabinoside, and quercetin-3-rhamnoside.
Caffeoylquinic acid and quercetin are powerful phenolic compounds that have been linked to protecting against several types of conditions, including, cardiovascular diseases, Alzheimer’s, cancer, gastric disorders, dyslipidemia, and hyperglycemia. On extraction with 50:50 water: methanol solvent system the anthocyanins were also isolated from the black walnut hulls.
Other nutrients found in ample amount in both Black and English walnuts are melatonin, folate, pectin, and various types of minerals such as phosphorous, calcium, magnesium, iron, manganese, potassium, silicon, selenium, and zinc. These components have been linked with improved lipid profiles, increased plasma antioxidant capacity, endothelial function, and neuroprotective action.
The predominant B vitamins like cobalamin (B12), folate (B9), and pyridoxal phosphate (B6) in walnuts exhibit a vital role in detoxifying methionine derived amino acid homocysteine which has atherothrombotic properties.
Finally, the black walnut contains slightly higher levels of arginine in comparison to the English walnut which has been related to lowering of blood pressure by acting as a precursor for the endogenous vasodilator, nitric oxide (NO) [3,4].
Fig 1: Chemical constituents present in the black walnut hull
The green hull of walnut was found as an economical source of antimicrobial agents. The juglone and other chemicals present in the hull have been shown to possess antibacterial activities and various published reports have confirmed its activity against Gram-positive and Gram-negative bacteria.
The antimicrobial potential of walnut hull extracts from various cultivars has been screened against Gram-positive (S. aureus, B. cereus, and B. subtilis) and Gram-negative (P. aeruginosa, E. coli, and Klebsiella pneumonia) bacteria, and fungi (Cryptococcus neoformans, and C. albicans). The results indicated that the growth of Gram-positive bacteria was inhibited by all the used walnut green husk extracts, and among them, S. aureus was found to be the most susceptible one. The minimum inhibitory concentration (MIC) of 0.1 mg/mL was reported for all the extracts .
Zamanter et al evaluated the antimicrobial potential of juglone (the main component present in the unripe hulls) against various pathogenic S. aureus strains isolated from the oral cavity of various children. Also, eight other reference strains (S. aureus, S. epidermidis, E. coli, Enterococcus feacalis, Salmonella enteric serovar Typhimurium, Vibrio alginolyticus, Pseudomonas aeruginosa, and B. cereus) were included in the study. Juglone demonstrated significant antibacterial activity against some strains of S. aureus with MICs values ranged from 64 to 128 µg/mL. The other S. aureus strains (B147, B295, B374, and B200) and nine reference strains were found resistant to juglone (MICs values ranged from 128-512 µg/mL).
Furthermore, the combination at 1/2-MIC of juglone with standard antibiotics such as tetracycline (Tet) and erythromycin (Ery) and disinfectant benzalkonium chloride (BC) has a significant decrease of MICs (2-8 fold potentiation) in the majority of tested strains. These combinations enhanced the antibacterial activity and the MICs values of Tet, Ery, and BC were reduced in comparison with the values attained when they were tested alone. Since BC, Tet, and Ery resistance is modulated by efflux pump systems, hence it is proposed that Juglone may act by blocking the respective efflux pumps (EPs) (bacterial membrane proteins notably in S. pneumonia, P. aeruginosa, and some other bacteria which extrude antibiotics and other antimicrobial agents out of the cell). Hence, Juglone has been reflected as a natural source for resistance-modifying activity in these bacteria and as a phytochemical constituent with antibiotic resistance-modifying activity .
Baghkheirati et al prepared silver chloride nanoparticles (AgCl NPs) using walnut green hull extract. The macromolecules present in the walnut green hull extract act as bioreducers and stabilizers in the prepared NPs. They contained additional bioactive molecules on their surface and demonstrated antibacterial activity against both Gram-positive and Gram-negative bacteria. Interestingly, the synthesized NPs showed considerable inhibitory effects against E. coli and S. aureus clinical isolates. It has also been reported that the antifungal and antibacterial activities of juglone nanoparticles are higher than free juglone, signifying that the nanoparticle formulation may be a promising method to enhance the beneficial effects of juglone .
Zhang et al evaluated the antimicrobial activities of various extracts of the walnut green hull against various bacterial and fungal strains by the Oxford cup method. All extracts showed different antimicrobial activities against Gram-positive (S. aureus, B. subtilis) bacteria, Gram-negative (E. coli, P. aeruginosa), and fungi (C. albicans, Penicillium italicum, Peniicilbum digitatum, Phytophthora capsici).
The walnut green husks extracted with chloroform and ethyl acetate exhibited the highest activities against the tested bacteria. In contrast, antifungal substances existed in petroleum ether extracts, with MIC against Penicillium italicum, Peniicilbum digitatum, and C. albicans about 3.13, 6.25, and 6.25 mg/mL respectively .
Helicobacter pylorus is a Gram-negative pathogenic bacterium associated with several human diseases, including peptic ulceration, gastritis, and gastric cancer. It is also reported that juglone can strongly inhibit H pylori growth at a low MIC of 1.6 µg/mL. Yun-hua et al found that juglone functions as a multitargeted inhibitor against, three key enzymes of Helicobacter pylori; malonyl-CoAacyl carrier protein transacylase (HpFabD), cystathionine γ-synthase (HpCGS), and β-hydroxyacyl-ACP dehydratase (HpFabZ) which provides some clues for the inhibitory mechanism underlying juglone’s anti-H pylori activity .
The mechanism for the toxic effects of juglone for various microbial strains may be different in various organisms. Many pathways have been proposed including decreased cell wall formation, enhanced membrane permeability, cell cycle disruption, cell death, inhibition of mRNA synthesis, DNA modifications (mainly in rapidly dividing cells), alkylation of amine or thiol groups of essential proteins, and decreasing levels of p53 (tumor suppressor). H+-ATPase inhibition is also a possible mechanism as well as K+ channel blocking.
The mechanisms of antibacterial and antifungal actions of juglone may also involve a process called redox cycling. Juglone can be reduced to form a semiquinone radical through the enzymes such as microsomal NADPH-cytochrome P450 reductase, microsomal NADH-cytochrome b5 reductase, and NADH-ubiquinone oxidoreductase in the cytoplasm or mitochondria. By the process of redox cycling, it is regenerated.
These semiquinones radicals of juglone react with molecular oxygen to produce superoxide (O2 ̄) and thereby hydrogen peroxide (H2O2), which is a strong oxidant creating a peroxidative environment in the cell and cause oxidative damage to the cell.
In comparison to other naphthoquinones, the high toxicity of juglone has been correlated to its high redox potential of -93mV. Juglone also has high thiol reactivity and electrophilicity which can cause irreversible complexation of vital proteins, expressly in cysteine-rich proteins that are important for mitosis [10,11].
The primary use of black walnut in herbal medicine is in the treatment of dermatophytic fungal infections. These infections usually involve keratinized tissues such as skin, hair, and nails. Microsporum, Trichophyton, and Epidermophyton species are among the microorganisms most commonly implicated as causative agents in dermatophytic fungal infections.
The unripe hulls of the black walnut have been used for many years in traditional medicine for the treatment of topical fungal infections e.g ringworm. The antifungal activity of walnut hulls has been credited to juglone. Alice et al compared the antifungal activity of juglone with eight other known antifungal compounds (clotrimazole, griseofulvin, tolnaftate, selenium sulfide, zinc undecylenate, liriodenine, and liriodenine methiodide) against the dermatophytes Trichophyton mentagrophytes and Microsporum gypseum.
Also, juglone was evaluated for its general antimicrobial activity against Gram-positive, Gram-negative, and acid-fast bacteria. The various microorganisms used were B. subtilis (ATCC 6633), S. aureus (ATCC 6538), E. coli (ATCC 10536), P. aeruginosa (ATCC 15442), Mycobacterium smegmatis (ATCC 607), C. albicans (ATCC 10231), Saccharomyces cerevisiae (ATCC 9763), Aspergillus niger (ATCC 16888), Trichophyton mentagrophytes (ATCC 9972), Helminthosporium sp. (NRRL 4671), Pycnoporus sanguineus (ATCC 14622) and Microsporum gypseum (ATCC 14683).
Screening was conducted by the agar well diffusion assay. From the MIC determinations, it was found that juglone has shown antifungal activity in comparison with commercial antifungal agents such as zinc undecylenate and selenium sulfide, However, it has also shown moderate antibacterial (Gram-positive) activity which may be significant since fungal skin infections are often escorted by secondary Gram-positive bacterial infections [12,13].
Parvin Abedi et al compared the antifungal effects of 2% and 4% black walnut hull extract with standard drug clotrimazole on C. albicans in rats. The results demonstrated that the 4% walnut extract eliminated C. albicans colony-forming units after 1 week of treatment, similar to the effects of clotrimazole . Grover et al. evaluated the effect of juglone on planktonic and sessile C. albicans cells. The results presented that a concentration of 160 µg/mL of juglone could expressively reduce the virality of colonies of C. albicans and has antibiofilm potential .
Rodrigues et al found the antifungal effect of the green husk of J. nigra and its use as an alternative for fluconazole against C. krusei, dermatophyte infections of the nails as well as skin and recurrent vaginal candidiasis . Salamat et al. also found in their study that the extract of walnut prevents the growth of C. albicans in a fraction of 337 mg/mL.
Black walnut hull is also useful in treating skin diseases including eczema, psoriasis, herpes, athlete’s foot (Tinea pedis), and skin parasites. It is specified, too, when there is a combination of gastrointestinal and skin issues as a result of an internal parasite or fungus, such as candida, pinworms, or tapeworms.
The chemical present in the black walnut can inhibit vital enzymes of yeasts which are needed for metabolic function, thus preventing it from growing and spreading. Juglone is a well-known inhibitor of peptidyl-prolyl cis/trans isomerase (PPIases) domain of Pin1 that accelerates the cis/trans isomerization of peptide bonds preceding prolyl residues. Pin1 modulates the activity of a protein that is phosphorylated to proline-directed serine or threonine residue (pSer/Thr-Pro). Recent studies have shown that Pin1 and its yeast homologue ESS1 are essential for the survival of Aspergillus nidulns, C. albicans, and Saccharomyces cerevisiae; and also been isolated from different organisms including, Drosophila melanogaster, Neurospora crassa, and Trypanosoma [18,19]
Parasitic organisms, like roundworms, tapeworms, pinworms, and many others, are often neglected and undiagnosed hence present a serious problem. These harmful organisms can enter the human body via contaminated food or water, mosquito bites, touching pets, and other animals, or any infected surface. On the finding of a suitable environment, they start to breed and, through various life cycles, can survive in the human intestinal tract for many years .
The black walnut hull is a powerful vermifuge (the substance that kills parasites). It contains high concentrations of natural iodine, astringent tannins, and compounds like juglone and plumbagin that have anthelmintic (worm-killing) properties. A decoction of the hull of black walnut has been used traditionally to expel worms. It helps expel intestinal worms, with species-specific effectiveness for ringworm (Tinea corporis).
Black walnut green hulls also eliminate parasites from extracellular fluids which include lymph and blood. The kidneys, liver, heart, and brain can also benefit from its antiparasitic action. More than 100 known parasites have been known to be killed by the black walnut hull. The black walnut tincture is generally used with two other anthelmintic herbs-cloves and wormwood. This combination is found effective against a broad range of intestinal worms and human parasites .
One in vitro studies study demonstrated that plumbagin inhibited the motility of and hatching of Haemonchus contortus first-stage larvae. Plumbagin was also found to larvicidal towards Ascaris suum at the highest test concentration (100 mM). However, the combination with other anthelmintic herbs would enhance the activity of plumbagin .
Acanthamoeba is a free-living amoeba usually distributed in the environment that can cause Acanthamoeba keratitis (AK); a rare infection of the cornea, and Granulomatous amoebic encephalitis (GAE) a fatal infection of the brain and spinal cord that occurs among immunocompromised persons. A study by Bijay kumar et al demonstrated that juglone significantly inhibited the growth of Acanthamoeba castellanii at 3-5 μM concentrations. Juglone increased the production of reactive oxygen species (ROS) such as, hydrogen peroxide, superoxide radical, and hydroxyl radical which causes oxidative stress and ultimately cell death .
Black walnut also works as a gentle laxative. Its ability to improve slow bowel transit time means it can be used as a remedy for chronic constipation and to flush out toxic buildup in the gut, which also helps with ridding the body of parasites.
Today, the black walnut hulls are used to help with various conditions. It is known to have laxative properties. Black walnut is known as an effective anti-viral and is used to fix warts, acne, and cold sores caused by the Herpes simplex virus.
It has been used as an antiseptic to combat illnesses like sexually transmitted infections and malaria and can be used to treat acne.
Black walnut hull is also used for lowering serum cholesterol levels and blood pressure and is alleged to burn up fatty materials and toxins while balancing blood sugar levels .
The tannins present in the hull have an astringent quality that is thought to shrink the sweat glands and decrease excessive sweating.
It also helps to control menorrhagia (prolonged and excessively heavy menstrual bleeding at regular menstrual cycle intervals).
The black walnut hull is considered a tonic that aids digestion and the intestinal system and is used to control diarrhea. It helps to relieve heartburn, colic, and flatulence.
It acts as a cholagogue, by stimulating the flow of bile into the intestines and is thought to ease cholelithiasis (gall stone attack) and pain in the spleen.
Walnut husk extracts can also inhibit enzyme xanthine oxidase, which is required for the synthesis of xanthine which causes hyperuricemia, a metabolic disorder causing inflammation and gout.
Juglone has also shown anti-cancer properties and decrease the probability of intestinal tumors in rats that have been exposed to carcinogens. It also demonstrated cytotoxic effects against cultured melanoma cells. It exerts its anticancer action via the formation of the semiquinone radical resulting in an increased concentration of reactive oxygen species (ROS) which leads to apoptosis .
Black walnuts can also be used as a bio‐herbicide. Traditionally, juglone has been used as a natural dye for fabrics and clothing, particularly wool, and as ink.
Because it tended to create dark orange-brown stains, juglone has also found use as a coloring agent for foods and cosmetics, such as hair dyes .
Fig 2: Various therapeutic uses of the black walnut hull
Preparations: It can be used in many ways, and can be taken internally or used externally. If taken internally, take 1-3 drops 1-3x/day, while an olive oil infusion of the crushed hulls can be used as the base for an anti-fungal salve. The powdered form can also be used in foot soaks, and as a wash for skin infections. As a tincture, black walnut can be applied topically to herpes and cold sores .
The external use of black walnut hulls poses little or no danger to the majority of people. However, in case of sensitivity to walnuts such as an allergic reaction or stomach irritation and upset, black walnut supplements should be avoided.
Tannins present in the black walnut may decrease the body’s ability to absorb other medications. Accordingly, black walnut supplements should not be consumed at the same time as regular medications. There must be a gap of 1-2 hr between taking the supplement and other medicines are the best way to ensure that they will all work effectively or in case of prescription medications .
Black walnut hulls are safe for occasional use of up to 2 weeks at a time and not recommended for long-term use.
Ingestion of large doses, cause sedation to the heart and circulatory system.
Furthermore, black walnut hulls will stain the skin on topical application, though the stain only lasts for a few days.
Persons with existing liver, kidney, or gastrointestinal conditions should take black walnut with caution as it can irritate.
Breastfeeding or pregnant women recommended not to take the supplements.
Furthermore, this supplement should be used under the care of a holistic health professional as black walnut is an extremely potent remedy .
Black walnut hull offers multiple health benefits such as antimicrobial, antihelmintic, antioxidant, cytotoxic based on its compositional profile.
Juglone, a phenolic compound found in walnuts, has been shown to exert both oxidant and antioxidant activities. When combined with an antibiotic or disinfectant, it enhances bacterial susceptibility to the respective drugs by inhibiting the efflux pump and leading to the accumulation of chemical compounds in the cells.
Therefore walnut hulls may be considered as a natural source of chemicals with antibiotic resistance modifying activity.
Dr. Harmeet Kaur received her Bachelors in Pharmacy from Guru Nanak Dev University in Amritsar, India in 2000. Guru Nanak Dev University is a state owned university with an "A" grade nationally.
Dr. Kaur received her Masters in Medicinal Chemistry from the National Institute of Pharmaceutical Education and Research in 2002.
In 2015 Dr. Kaur was awarded her Ph.D in Pharmaceutical Sciences from Maharshi Dayanad University in Rohtak, India.
Dr. Kaur is presently a Senior Research Scientist at Maharshi Dayanand University in India.
Dr. Kaur has over 35 published Research papers concerning infectious diseases caused by yeasts, fungi, and bacteria using both prescription drugs and natural plant compounds. She has also performed many studies on cancer cells.
Of particular importance to us, is her multiple experiments performed on Candida albicans and pathogenic bacteria using natural compounds. Because of this experience, she is more than qualified to write any article concerning the effects of herbs against yeast and bacteria on this website.
If you have any questions about black walnut hull or yeast infections in general, please feel free to contact us from the contact page of this website.
Dr. Kaur's Medical References:
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