Abstract: This review focuses on the efficacy and safety of medicinal plants which have been utilized in traditional medicine for anti-aging purpose. All relevant databases were searched for the terms “anti-aging” and “herbs” or “medicinal plant” without limitation up to 30th January 2011. All the clinical and non-clinical studies with the outcome of change in aging process were included. Search in databases resulted in 1733 articles that on the basis of inclusion/exclusion criteria, 67 studies were finally included. Six human and 61 animal studies were reviewed for the effect of anti-aging herbs on aging process. Most of the studies showed significant improvement in brain function (memory, cognitive, anxiety), sexual disorder and skin wrinkle. From the performed studies, the exact mechanism of anti-aging action and side effect cannot be concluded and thus further studies would be helpful.
INTRODUCTION
Aging is a biological phenomenon of life that leads to progressive and deadly changes in organisms. Approximately 100,000 people worldwide die every day because of age-related problems (De Grey, 2007). Though neuron loss is minor after 20 years of age, there is a 10% decrease each decade in the total length of the brain’s myelinated axons (Marner et al., 2003). A lot of theories propose that aging results from the accumulation of damage at different levels of organ, cell and cell nucleus. Various theories have been proposed in the aging process but the general ones refer to free-radicals, cross-linkage, reliability theory of aging and longevity, somatic mutation, accumulative-waste, aging-clock, the viral theory and etc. Amongst these theories, most of scientists are in favor of free radical theory (Momtaz and Abdollahi, 2012). Studies show that increasing Reactive Oxygen Species (ROS) has a key role in oxidative damage of major cellular elements such as protein, lipid and DNA resulting in deterioration of energy production, multi-organ failure, aging and death. The antioxidant defense system consists of free radical scavenging enzymes such as catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD) and antioxidants such as vitamin C, vitamin E and etc. An imbalance that is caused by increased generation of free radicals or reduced functional efficiency of antioxidant defense system is believed as one of the primary factors contributing to aging (Momtaz and Abdollahi, 2012). From ancient time, people were interested and tried to keep themselves young. Therefore, anti-aging study is certainly not a new research area and has traditional links. Nowadays, the meaning of anti-aging has changed from simply prolonging lifespan to increasing health span which emphasizes more on the quality of life. Herbal medicine has a long history in Asian countries. It is believed that many of the medicinal herbs have anti-aging properties. Recent studies have shown that some medicinal herbs are effective in intervention or prevention of aging-related disorders. In this review, we have focused on anti-aging herbs and their characteristics in different clinical or experimental models.
MATERIALS AND METHODS
All relevant databases like Google scholar, Scopus, Iranmedex and Pubmed were searched up to 30th January 2011 for studies examined effect of anti-aging herbs on aging process. The search terms were anti-aging and herbs, medicinal plants or herbal medicine without any limitation. A flow diagram of search process has been demonstrated in Fig. 1. Among the studies, 6 were on human and 61 on animals. Two reviewers independently examined all papers to ensure the title, abstract and references of each article to eliminate duplication. The reference list of each article was reviewed for additional relevant studies. Letter to editor, review articles, or dissertations were not included. The included papers were summarized according to dose, treatment duration, grouping, main outcome, probable mechanism and side effects (Table 1).
RESULTS
The initial search identified 1733 articles, from which 67 studies met inclusion criteria and were reviewed (Table 1). The search process is shown in Fig. 1. Herbs such as Lycium barbarum (wolfberry {goji berry}), Nardostachys jatamansi, Phragmites communis, Ginkgo (total lactone), Astragalus membranaceus (hairy root), Curcumin pointed to have anti-oxidant effects. Wolfberry (Lycium barbrum) is the fruit of the plant Lycium barbarum that grows in China or Vietnam contains powerful antioxidant with anti-aging properties such as vitamins B1, B6 and E. Anti-oxidant effect of Licuim barbarm (wolfberry or gojiberry) was demonstrated by its ability to improve body antioxidant power and immune function and reduction of Lipid Peroxides (LPO).
| Fig. 1: | Flow diagram of the search process. |
| Table 1: | Human and animal studies considering anti-aging effects of medicinal plants |
| Abreviations: d: Day, w: week, m: month, g: Gram, sc: Subcutaneus, Sig: Significant, PFC: prefrontal cortex, MMPs: Matrix Metalloproteinases, Inj: Injection, MDA: malondialdehyde, NO: nitrogen oxide. NH(3): Amonia, SOD: superoxide dismutase, CAT: catalase, GSH: glutathione, TAOC: total antioxidant capacity, GSH-Px: glutathione peroxidase, LPO: Lipid Peroxide, MAO: Monoamine oxidase, SAMP8: senescence accelerated mice, AA: arachidonic acid, SI: the saturation index saturated/polyunsaturated species), SAP: (Stretched Attend Posture), SAM: a novel strain of Senescence Accelerated Mouse, ip: intraperitoneal, SOA: Super Oxide Anion, wt: weight, FBS: fasting blood sugar, HbA1c: Glycated Hemoglobin, Chol: Cholesterol, Tg: Triglyceride, PUFA: poly unsaturated fatty acid, EPA: eicosa pantaenoic acid, NK cell: natural killer cell, Ach-E: acetyl cholinesterase, Ach: acetyl choline | |
Lycium barbarum (wolfberry or gojiberry) has been considered in anti-aging trials more than other herbs. Some studies pointed to mood stabilizing and anti-anxiety effects and effective improvement of cognitive disorders (dementia and Alzheimer’s disease) (Joshi and Parle, 2006a; Bhattacharya et al., 2000; Pardon et al., 2006; Naderi et al., 2010; Shin et al., 2009). Eight studies noticed enhancement of stem cell production, restoration of impaired immune functions of old mice in terms of number of T cells and Natural Killer (NK) cells and antibody response. One animal study showed that Panax ginseng (red ginseng) significantly inhibits wrinkle formation (Kang et al., 2009). This herb inhibits degradation of collagen. Another study on sexual behavior showed that Epimedium koreanum improved erectile function (Makarova et al., 2007).
Human studies consisted of 6 articles (Gim et al., 2009; Tian et al., 1997; Yonei et al., 2008; Sugiyama, 2006; Amagase and Nance, 2008; Lee et al., 2008). Two studies revealed improvement of blood LPO, fasting blood sugar and glycated hemoglobin (HbA1c) (Tian et al., 1997; Yonei et al., 2008) while three studies (Sugiyama, 2006; Amagase and Nance, 2008; Lee et al., 2008) referred to subjective feeling of well-being and improvement in neurologic/psychologic performance of cognitive subscale confirmed by Mini-mental State Examination (MMSE) and Alzheimer disease assessment scale (ADAS).
DISCUSSION
Most of included studies concluded that some of herbs can significantly delay process of aging mostly in the organs like brain, vascular systems, skin and sex. Number of studies performed in humans is too few in comparison to that of animals. If the included papers are detailed, they can be divided into four categories in terms of proposed mechanism of action of the tested herb such as anti-oxidant effect, anti-inflammatory effect, effect on (memory, cognitive and mood) and stimulatory effect on sex hormones (Fig. 2).
| Fig. 2: | Suggested machanisms of action of herbs in reducing aging process |
The most effective herb that had anti-oxidant effect was Licium barbarum (wolfberry or gojiberry) that significantly raised body SOD, CAT and reduced LPO (Li, 2007). Diseases which increase in frequency with age include arthritis, osteoporosis, heart disease, cancer, Alzheimer’s, diabetes, etc. Animal cells have three important enzymes to deal with the free radicals including SOD, GPx and CAT.
Other herbs that showed anti-aging effect with the same mechanism includes Phragmites communis polysaccharide (Qin et al., 2008; Miao et al., 2004; Dong et al., 2004; Yang et al., 2000) and Garcinia cambogia Tianwang Buxin Pills (TBPs) that significantly improved blood LPO but raised total cholesterol, Fasting Blood glucose (FBS) and Hemoglobin A1c (HbA1c). In addition, physical symptoms improved but not significantly.
Yokukansan (YKS) significantly Improved anxiety-related responses and decreased serotonin and dopamine in the Prefrontal Cortex (PFC) and reduced plasma ammonia (NH3) (Mizoguchi et al., 2010).
Kami-Untan-To (KUT) significantly increased brain Acetylcholine (ACh) and the density of Choline Acetyltransferase (ChAT) immunoreactive cells (Wang et al., 2000).
Hibiscus sabdariffa Linn (calyces) decreased whole brain acetyl cholinesterase (AChE) activity (Joshi and Parle, 2006c). In two human studies, use of Panax ginseng powder and Tong Jiang oral liquid with Da Huang (radix et Rhizoma rhei) improved cognitive subscale (MMSE) and ADAS. After discontinuing ginseng, scores declined to the levels of controls (Tian et al., 1997; Lee et al., 2008).
Besides in some studies, herbs such as Hachimi-jio-gan a traditional Japanese herbal medicine (Furuya et al., 2002), Hochu-ekki-to (TJ-41) (Utsuyama et al., 2001), Echinacea purpurea (Currier and Miller, 2000), gerbils (Rabin et al., 1998) and Atractylis macrocephal Koidz (Mao et al., 1996) totally caused immunoboosting effect by increasing the number of T cells and NK cells and antibody response.
Toki-Shakuyaku-San (PaeoniaeRadix) (Komatsu et al., 1999) in the females elevated senescence-accelerated mice (SAMP8), concentrations of gamma-aminobutyric acid (GABA), alanine and glycine.
Taking collectively, most of anti-aging herbals have antioxidant components. In the recent years, role of oxidative stress and benefit of antioxidants in most of aging-related illnesses have been reviewed. For instance diabetes (Rahimi et al., 2005; Hasani-Ranjbar et al., 2009; Mohseni-Salehi-Monfared et al., 2009; Larijani et al., 2011), osteoporosis (Abdollahi et al., 2005; Yousefzadeh et al., 2006), illnesses from chronic exposure to environmental toxins (Abdollahi et al., 2004; Malekirad et al., 2005), inflammatory bowel disease (Rahimi et al., 2009; Rezaie et al., 2007), hyperlipidemia (Hasani-Ranjbar et al., 2010; Momtaz and Abdollahi, 2010) can be exampled.
Our study had some strengths and limitations. As an advantage, we conducted this review for the first time by examining all studies which tested herbs as anti-aging. Unfortunately, adverse effects have not been described in most of these studies. We acknowledge that there are really few number of clinical trials and those existing have low quality or are not homogeny and thus reaching a definitive conclusion is hard. Of course results of this study clarified these limitations and may help researchers to better design future trials.
ACKNOWLEDGMENT
This study, is the outcome of an in-house non-financially supported study.