Clinical Studies and References

Ashwaganda

Studies on the immunomodulatory effects of Ashwagandha.
Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B.
Medinova Diagnostics Center, Indian Drugs Research Association, Pune, India.
AJ Ethnopharmacol. 1996 Feb;50(2):69-76. PMID: 8866726[Read the Abstract]
Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study.
Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S.
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University
Phytomedicine. 2000 Dec;7(6):463-9. PMID: 11194174 [Read the Abstract]
Search for natural products related to regeneration of the neuronal network.
Tohda C, Kuboyama T, Komatsu K.
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, Japan.
Neurosignals. 2005;14(1-2):34-45 PMID: 15956813 [Read the Abstract]

Withania somnifera (ashwagandha) - monograph.
Altern Med Rev. 2004 Jun;9(2):211-214.
Withania somnifera, also known as ashwagandha, Indian ginseng, or winter cherry, has been an important herb in the Ayurvedic and indigenous medical systems for over 3000 years. Historically, the plant has been used as an aphrodisiac, liver tonic, anti-inflammatory agent,  and more recently to treat asthma, ulcers, insomnia, and senile dementia. Clinical trials and animal research support the use of ashwagandha for anxiety, cognitive and neurological disorders, inflammation, and Parkinson's disease. Ashwagandha's chemopreventive properties make it a potentially useful adjunct for patients undergoing radiation and chemotherapy. Ashwaganda is also used therapeutically as an adaptogen for patients with nervous exhaustion, and debility due to stress, and as an immune stimulant in patients with low white blood cell counts.

 

Shatavari

Indian Journal of Medicinal Science
Goyal RK, Singh J, Lal Harbans
Pt. B. D. Sharma Post Graduate Institute of Medical Science, Rohtak, Haryana, India
Abstract
Asparagus racemosus (Shatavari) is recommended in Ayurvedic texts for prevention and treatment of gastric ulcers, dyspepsia and as a galactogogue. A. racemosus has also been used successfully by some Ayurvedic practitioners for nervous disorders, inflammation, liver diseases and certain infectious diseases. However, no scientific proof justifying aforementioned uses of root extract of A. racemosus is available so far. Recently few reports are available demonstrating beneficial effects of alcoholic and water extracts of the root of A. racemosus in some clinical conditions and experimentally induced diseases, e.g. galactogogue effect, antihepatotoxic and immunomodulatory activities. The present article includes the detailed exploration of pharmacological properties of the root extract of A. racemosus reported so far.

Chopra RN, Chopra IC, Handa KL, Kapur LD.Indigenous drugs of India. Calcutta: Academic Publishers; 1994. pp. 496.

Oketch-Rabah HA. Phytochemical Constituents of the Genus Asparagus and their biological activities. Hamdard 1998;41:33-43

Roy RN, Bhagwager S, Chavan SR, Dutta NK. Preliminary pharmacological studies on extracts of Root of Asparagus racemosus (Satavari), Willd, N.O. Lilliaceae. J Res Ind Med 1971;6:132-8.

Muruganadan S, Garg H, Lal J, Chandra S, Kumar D. Studies on the immunostimulant and antihepatotoxic activities of Asparagus racemosus root extract. J Med Arom PI Sci 2000;22:49-52.

 

L-Theanine
l-Theanine reduces psychological and physiological stress responses.
Biol Psychol. 2006 Aug 21; Nagoya University Department of Psychology, Chikusa-ku, Nagoya, 464-8601, Japan.
Because the characteristics of l-Theanine suggest that it may influence psychological and physiological states under stress, the present study examined these possible effects in a laboratory setting using a mental arithmetic task as an acute stressor. Twelve participants underwent four separate trials: one in which they took l-Theanine at the start of an experimental procedure, one in which they took l-Theanine midway, and two control trials in which they either took a placebo or nothing. The experimental sessions were performed by double-blind, and the order of them was counterbalanced. The results showed that l-Theanine intake resulted in a reduction in the heart rate (HR) and salivary immunoglobulin A (s-IgA) responses to an acute stress task relative to the placebo control condition. Moreover, analyses of heart rate variability indicated that the reductions in HR and s-IgA were likely attributable to an attenuation of sympathetic nervous activation. Thus, it was suggested that the oral intake of l-Theanine could cause anti-stress effects via the inhibition of cortical neuron excitation.  l-Theanine reduces psychological and physiological stress responses.
 

L-Tyrosine
Lack of behavioural effects after acute tyrosine depletion in healthy volunteers.
J Psychopharmacol. 2005 Jan;19(1):5-11.
Acute dietary l tyrosine depletion has previously been shown to reduce dopamine neurotransmission in both animals and humans. In this study, we investigated the effects of brain dopamine depletion, through acute l-tyrosine and phenylalanine depletion, on plasma prolactin, mood and neuropsychological function in 12 normal subjects. In a randomized, double-blind, cross-over design, subjects received two amino-acid drinks separated by a week, a nutritionally balanced mixture (Bal) and on the other occasion a tyrosine and phenylalanine deficient mixture. The plasma ratio of tyrosine and phenylalanine to the other large neutral amino acids decreased significantly on the tyrosine and phenylalanine deficient mixture and there was an increase in plasma prolactin concentration relative to the balanced drink in the seven subjects for whom results were available for both occasions. Acute tyrosine depletion did not alter mood as measured by visual analogue scale ratings, and measures of memory, attention and behavioural inhibition were also unaffected. Our results are consistent with acute dietary tyrosine depletion causing a reduction in brain dopamine neurotransmission but raise questions about how robust or consistent the effects are on psychological function.

 

Gotu Kola

Bradwejn J, et al. A double-blind placebo-controlled study on the effects of gotu kola on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4.
An evaluation of the effects of gotu kola on the acoustic startle response (ASR) in humans. Subjects were randomly assigned to receive either a single 12 g orally administered dose of gotu kola (n=20) or placebo (n=20). Gotu kola significantly attenuated the peak ASR amplitude 30 and 60 minutes after treatment.

Wattanathorn J, et al. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol. Mar 5 2008;116(2):325-332.
In this randomized, placebo-controlled, double-blind study, 28 participants (> 61 years of age) received either gotu kola extracts (250, 500, or 750 mg daily) or placebo in order to determine the effect of gotu kola on cognitive function and mood. After 2 months, cognitive function (as assessed by event-related potential and the computerized assessment battery test) and mood (using Bond-Lader visual analogue) was determined. The greatest improvements in mood and cognitive function were detected in those receiving the 750 mg dose of gotu kola. Further long-term studies will help determine the mechanism by which gotu kola influences age-related changes in mood and cognitive function.
 
Wattanathorn J, Mator L, Muchimapura S, et al. Positive modulation of cognition and mood in the healthy elderly volunteer following the administration of Centella asiatica. J Ethnopharmacol. Mar 5 2008;116(2):325-332.

DerMarderosian A, editor. The Review of Natural Products. St. Louis: Facts and Comparisons; 1999.
Bradwein J, et al. A double-blind, placebo-controlled study on the effects of gotu kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4.

 

 

Alpha Lipoic Acid

Neuroprotection by the Metabolic Antioxidant Image-Lipoic Acid
Lester Packer, Hans J. Tritschler and Klaus Wessel
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3200 USA
ASTA Medica AG, 45 Weismullerstraße, D-60314, Frankfurt am Main, Germany, 1996
Abstract
Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant Image-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6,8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood–brain barrier. Image-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both Image-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of Image-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas Image-lipoic acid can. In vitro, animal, and preliminary human studies indicate that Image-lipoate may be effective in numerous neurodegenerative disorders. Copyright © 1996

Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Rad Bio Med. 1995;19(2):227-250.

Lynch MA. Lipoic acid confers protection against oxidative injury in non-neuronal and neuronal tissue. Nutr Neurosci. 2001;4(6):419-438.

Nagamatsu M, Nickander KK, Schmelzer JD,et al. Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care. 1995;18:1160-1167.

 

Bai Zi Ren
Li Shu Zhi, et al. The chemical composition of Bai Zi Ren oil. Journal of Chinese Patent Medicine. 1999;21(2):88-89.

Chu Peng Jiang. Bai Zi Ren's effect on passive avoidance learning in mice with damage in forebrain's basal nuclei. Foreign Medicine,vol. of TCM. 1993;15(2):40

 

Ling Zhi
Yang, QY and Wang, MM. (1995). The effect of ganoderma lucidum extract against fatigue and endurance in the absence of oxygen. In Proc. Contributed. Symposium. 59A, B.2. Role of Ganoderma Supplementation in Cancer Management

Chang, R. (1994). Effective dose of ganoderma in humans. In Proc. Contributed Symposium 59A, B. 5th Intl. Mycol. Congr., Buchanan PK, Hseu RS and Moncalvo JM (eds), Taipei, p. 101-13

Sliva D, Sedlak M, Slivova V, Valachovicova T, Lloyd FP Jr. and Ho Nw. Biologic activity spores and dried powder from Ganoderma lucidum for the inhibition of a highly invasive human breast and prostate cancer cells. J Altern Complement Med. 2003; 9:491-

Cheng JJ, Zeng YS, Xiong Y, Zhang W, Chen SJ, Zhong ZQ. Division of Neuroscience, Department of Histology and Embryology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou Ganoderma spores may regulate the levels of mitochondria-related molecular substances in hippocampus of young rats birthed by rats with gestational hypertension.Zhong Xi Yi Jie He Xue Bao. 2007 May;5(3):322-7

Wong KL et al
Antioxidant activity of ganoderma lucidum (reishi) in acute ethanol-induced heart toxicity.
Phytother Res. 2004 Dec;18(12):1024-6.