Function

Saw Palmetto

Saw palmetto is indigenous to the southeastern United States. Historically, it was used by Native Americans to treat genitourinary symptoms, relieve inflamed mucous membranes, increase testicular function and increase breast size.[1] The extract is currently a popular supplement for treating benign prostatic hyperplasia (BPH) and those diagnosed with prostate cancer. Saw palmetto has been shown to inhibit 5a-reductase, an enzyme that converts testosterone to dihydrotestosterone.[2] Saw palmetto extracts are approximately 90% fatty acids and are rich in saturated, medium-chain fatty acids, myristate, and laurate. Studies have proposed that fatty acids may be responsible for inhibiting 5a-reductase, but which one(s) is unknown.[2] Saw palmetto also demonstrates a-adrenoceptor, muscarinic, and 1,4-dihydropyridine inhibitory properties.[1]

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Garlic

Garlic (Allium sativum) is among the most researched herbal supplements and is the second most used complementary therapy.[3] In the US, it has primarily been used to reduce hypercholesterolemia and hypertension. Studies have shown that it has hepatoprotective, neuroprotective, and antioxidant properties.[4] In several studies, S-allylcysteine (SAC), a compound found in garlic, showed neuroprotective and cardioprotective properties by inhibiting cell damage in the heart, neuron, and endothelium.[4] SAC has also been shown to destabilize A-beta-fibrils found in Alzheimer disease.[5] In rats with brain ischemia, SAC has been shown to inhibit free radical production, neuronal damage, and lipid peroxidation. In severely hypertensive patients, garlic was shown to reduce blood pressure and cardiovascular events.[6][7] S-propyl-L-cysteine (SPC), a structural analog of SAC, has been shown to reverse gastric cancer in mice.[8] Allicin is a compound in garlic that is produced after it is chopped or crushed. A daily dose of 0.5g to 1.5g of allicin significantly reduced HbA1c levels in Type 2 diabetics within 12 weeks.[7]

Gingko Biloba

Ginkgo biloba is commonly used to improve memory and cognition in the elderly suffering from impaired cerebral circulation. Mitochondrial dysfunction is one theory proposed as the leading cause of cognitive decline.[9] The two main components in Gingko biloba leaves are flavonoids and terpene trilactones.[9] Together, these compounds enhance and protect mitochondrial function and scavenge reactive molecules like hydroxyl and peroxyl radicals, nitric oxide, and superoxide ions.[9] Treatment with Gingko biloba significantly improved cognitive function in dementia patients.[10] It is also effective as adjunctive therapy for chronic schizophrenia patients.[9] New research has shown a positive effect on Alzheimer patients that supplement with Gingko biloba. Specifically, Gingko biloba was shown to improve endocrine homeostasis, regulate hormone sensitivity, maintain endothelial microvascular integrity, and proteolyze tau proteins.[11] However, Gingko biloba was ineffective in improving concentration, memory, or executive function in healthy patients.[9]

Echinacea

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Echinacea is a native species to eastern and central North America. Historically, Native Americans used Echinacea for treating colds, bronchitis, flu, and respiratory infections.[12] Echinacea is known as an immunostimulant, boosting both innate and specific immunity. It has also demonstrated antiviral, anti-inflammatory, and antimicrobial effects.[12] In the bone marrow of mice, Echinacea extract significantly increased expression of CD80, CD86, and MHCII, upregulated markers of classically activated macrophages (M1), and the production of IL-6 IL-12p70, IL-1beta, nitrous oxide (NO), and TNF-a. Intracellular bactericidal activity and enhanced phagocytosis were also observed.[12] A randomized, double-blind study of 473 patients virologically confirmed with influenza infection showed Echinacea was as effective as oseltamivir with fewer adverse events and reduced risk.[13]

Black Cohosh

Black cohosh (Actaea racemosa) is commonly used to treat premenstrual syndrome (PMS), dysmenorrhea, menopausal symptoms, and in particular, hot flashes. It has also seen increased use in women who have breast cancer.[14] Its increased use may, in part, be because of studies from the Women’s Health Initiative showing traditional hormone replacement therapy increased the risk of breast cancer and negative cardiovascular consequences.[15] Black cohosh has been shown to have selective estrogen receptor modulator properties, but the specific compounds that impart this effect are as yet undetermined. Triterpene glycosides are one group suggested as the compounds responsible.[14] Cycloartane triterpenoids found in black cohosh induced mitochondrial apoptosis and cell arrest.[14] Actein, also found in black cohosh, showed antiangiogenic effects. A dose of 10 mg/kg of oral actin for seven days inhibited blood vessel formation. The same dose given orally for 28 days decreased breast tumor size and metastasis to the lungs and liver in mice.[14] Black cohosh’s efficacy in reducing hot flashes and controlling vasomotor symptoms has been shown in comprehensive studies.[16]

Ginseng

Ginseng is used commonly to boost energy, enhance physical and mental performance, treat erectile dysfunction, and strengthen the immune response. Ginseng is a generic term that represents several species in the genus Panax. These include Panax quinquefolius L (American ginseng), Panax ginseng, and Panax japonicus (Asian ginseng). Ginseng is composed of a diverse amount of active compounds that affect many metabolic pathways. Of those, ginsenosides have been shown to have clinical significance. They are found in the plant’s roots but have also been reported to be abundant in the berries.[17] Ginsenosides have been shown to activate macrophages and natural killer cells primarily responsible for innate immunity. They also regulate immunocytes and cytokines, which affect cell-mediated and humoral immunity.[18] In the prevention of fatigue, ginseng was shown to increase recovery of creatinine kinase, decrease IL-6 and increase insulin sensitivity.[18] Ginseng has shown antiproliferative effects in breast cancer.[14] It has also been shown to effectively treat chronic kidney disease, non-small-cell lung cancer, acute respiratory distress syndrome, and septic acute lung injury.[19]

Ginsenosides and their metabolites are known to modulate signaling pathways of metastasis, angiogenesis, inflammation, oxidative stress, and stem/progenitor-like properties in breast cancer cells.[14] For example, ginsenoside Rp 1 induced cycle arrest and apoptosis in cancer cells.[14] Another promising effect ginsenosides had on cancer cells was increasing the sensitivity of those cells to anticancer drugs. By downregulating the RNA level of MDR-1, it increased sensitivity to gemcitabine, cisplatin, paclitaxel, and epirubicin.[14] For erectile dysfunction, ginsenosides have been shown to increase nitric oxide activity in endothelial cells in vitro, relaxing the smooth muscles of the corpus cavernosum.[20][17] A dose of 1.5 g of red ginseng powder daily for 12 weeks to varicocele patients improved the number, motility, and shape of spermatozoa compared to control groups.[18]

Hawthorn

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Hawthorn (Crataegus monogyna) is commonly used for heart-related conditions, specifically as a supportive treatment for angina, atherosclerosis, heart failure, angina, atherosclerosis, and high blood pressure. Hawthorn’s effects on the heart were first reported in the first century AD and have been well established.[21] WS 1442 and LI 132 extracts have been the most studied compounds of hawthorn and come from the flowers and leaves of the plant. The WS 1442 extract contains oligomeric procyanidins(OPC), which have been shown to act as free radical scavengers.[21] They have also been shown to inhibit human neutrophil elastase which is released from activated leukocytes in previously ischemic myocardium after restoring blood flow.[21] OPCs also increase coronary blood flow, improving endothelium function.[21] WS 1442 extract showed reduced ST-segment elevation on ECG, reduced incidence of ventricular arrhythmias, size of infarction zone, and mortality in pre-treated animals.[21] Long-term administration of WS 1442 was shown to increase myocardial basal vessel blood flow.[22] It prevented alterations of cardiac, renal, and vascular function and structure and deoxycorticosterone acetate (DOCA) salt-induced hypertension.[22]

St. John’s Wort

St. John’s Wort (Hypericum perforatum) is commonly used to treat mild-to-moderate depression. St. John’s Wort as a medicinal herb is traceable back to the ancient Greeks who used it to treat burns, as an astringent to arrest diarrhea, and as a diuretic.[23][24] Several bioactive compounds have been identified in St. John’s Wort that work synergistically to provide its antidepressant and anti-inflammatory attributes.[23] These include phenolic acids, flavonoids (quercetin, isoquercitrin, quercitrin, epigenanin, rutin, hyperoside), hyperforin, and hypericin.[23] These compounds have been shown to affect neurotransmitters like N-methyl-D-aspartic acid (NMDA), g-aminobutyric acid (GABA), and serotonin receptors.[25]

At a daily dosage of 300 to 1200 mg, St. John’s Wort was more efficacious than standard antidepressant therapy in patients with mild-to-moderate depression.[25] St. John’s Wort extracts were shown to reduce PGE2 and NO production from macrophages by more than 30% in mice.[26] Hyperforin and hypericin, along with other compounds found in St. John’s Wort, were found to be active against gram-positive and gram-negative bacteria.[24] St. John’s Wort is active against multi-drug resistant bacteria, with extracts imparting potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA).[27]

Goldenseal

Goldenseal (Hydrastis canadensis) has long been used for its antiseptic qualities and activity against colds, the flu, and inflammation of the nares. It is indigenous to eastern North America and southeastern Canada. Native Americans used the roots of goldenseal to treat skin and eye infections and gastrointestinal irritation.[28] The primary compounds that have shown biological activity are beta-hydrastine and berberine.[29] 6-desmethyl sideroxylon, sideroxylon, and 8-desmethyl sideroxylon were noted to enhance the antimicrobial activity of goldenseal alkaloids (berberine).[28] These compounds, known as flavonoids, inhibit bacterial efflux pumps, allowing berberine to accumulate in bacterial cells.[28] Leaf extracts of goldenseal were shown to have antimicrobial activity against MRSA.[30] They reduced alpha-toxin production from Staphylococcus aureus, preventing damage to human skin keratinocytes.[30] Goldenseal extracts also showed antimicrobial activity against multiple drug-resistant strains of Mycobacterium species, including M. tuberculosis.[31] Berberine has demonstrated antiviral activity against Herpes simplex virus 1 and 2 by modulating host cell activation of the NF-kB and MAPK pathways.[32]

Feverfew

Feverfew (Tanacetum parthenium) is commonly used for migraine headaches and menstrual cramps. It is native to Asia Minor but cultivated worldwide. Major active compounds found in feverfew include sesquiterpene lactones, 3b-hydroxy parthenolide, parthenolide, canin, and artecanin.[33] Of these, parthenolide has been shown to have the most biological activity.[33] It is highest in concentration in the leaves and flowers of the plant.[33] Parthenolides have shown efficacy in preventing migraines.[34] Its antimigraine properties include inhibiting serotonin release from platelets, vascular smooth muscle relaxation, and anti-inflammatory effects.[34] Chrysanthenyl acetate, found in feverfew essential oil, was shown to inhibit prostaglandins and have analgesic properties.[35] Parthenolide has demonstrated nephroprotective qualities by inhibiting free radical production from CCL metabolism.[33] Parthenolide has also been shown to inactivate JAKs, consequently blocking STAT3 signaling that leads to the arrest of the growth and migration of cancer cells.[36]

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