Efficacy and Safety of Standardized Extract of Trigonella foenum-graecum L Seeds as an Adjuvant to L-Dopa in the Management of Patients with Parkinson’s Disease J. Nathan, 1 Siddika Panjwani, 1 V. Mohan, 2 Veena Joshi 2 and Prasad Arvind Thakurdesai 2 * 1 Movement Disorder Clinic, Shushrusha Hospital, 698B, Ranade Road, Shivaji Park, Dadar (West), Mumbai 400028, India 2 Department of scientific affairs, Indus Biotech Private Limited, 1, Rahul Residency, Off Salunke Vihar Road, Kondhwa, Pune 411 048, India The objective of this study is to evaluate disease modifying efficacy and safety of a standardized extract of Trigonella foenum-graecum L, Fenugreek (IBHB) (family Fabaceae) as a nutritional adjuvant to Levo-dopa (L-Dopa) in Parkinson’s disease (PD) patients. We conducted double-blind placebo-controlled proof of concept clinical study of IBHB capsules (300 mg, twice daily) with matching placebo for 6 months of period in 50 patients of PD stabilized on L-Dopa therapy. The efficacy outcome measures were the scores of Unified Parkinson’s Disease Rating Scale (UPDRS - total and its subsections), and Hoehn and Yahr (H&Y) staging at baseline and end of 6-months treatment duration. Safety evaluation included haematology, biochemistry, urinalysis parameters and adverse event monitoring. Total UPDRS scores in IBHB treatment (0.098%) showed slower rise as opposed to steep rise (13.36%) shown by placebo. Further, Clinically Important Difference for total UPDRS scores and scores of motor subsection of UPDRS was found to be 5.3 and 4.8, respectively, in favour of IBHB treatment. Similar improvement was shown by IBHB in terms of H&Y staging as compared with placebo. IBHB was found to have excellent safety and tolerability profile. In conclusion, IBHB can be useful adjuvant treatment with L-Dopa in management of PD patients. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: Trigonella foenum-graecum; fenugreek; Parkinson’s disease; UPDRS; Hoehn and Yahr (H&Y) staging; Trigonelline. INTRODUCTION Parkinson’s disease (PD) is a progressive, neurodegen- erative disorder affecting mainly dopaminergic neuronal systems with impaired motor function as a consequence. However other symptoms like neuropsychiatric prob- lems, autonomic dysfunction and sleep disorders may occur. Despite the great number of ongoing investiga- tions, neurodegenerative diseases including PD remain incurable. Current therapy for PD is essentially symptomatic. Use of Levo-dopa (L-Dopa), the direct precursor of dopamine, remaining the primary treatment choice since its first use over 30 years ago (Markham and Diamond, 1981; Silva et al., 1997). The major clinical symptom, i.e. the inability to initiate voluntary move- ments, can be relieved by L-Dopa (Cotzias et al., 1969). However, a major problem of L-Dopa therapy is the maintenance of a good responsiveness to the drug during long-term therapy (Ruberg et al., 1995). The success of long-term L-Dopa therapy in PD is compromised by the almost invariable intrusion of dyskinesias during the periods of the day when medica- tion is at its most effective (Cotzias et al., 1969). After treatment with the drug for more than 5 or 6 years, a majority of patients develop response fluctuations, dys- kinesia or dystonia (Goberman and Blomgren, 2003; Papapetropoulos et al., 2007; Shif and Kempster, 1994) Neuroprotective therapy to rescue dopamine neurons, which could alter and prevent the progression of PD (Dunnett and Bjorklund, 1999), has been proposed as an alternative to symptomatic treatment. The selective MAO-B inhibitors drugs currently available are efficacious in the prolonging the need of L-Dopa treatment, but do not prevent or reverse the underlying neurodegeneration. Only limited amount of neuroprotection can be observed in the animal models of PD with MAO-B inhibitors (Tuite and Riss, 2003). Neuroprotective properties for selegiline have been suggested (Heikkila et al., 1984) but have been proven. Therefore, novel treatments with neuroprotective action, which could alleviate motor dys- function in PD at an early stage and also delay the use of L-Dopa, are in need. Such treatment will be useful to reduce the fluctuation in the effects of L-Dopa use in late stage of PD by lengthening its duration of action and therefore diminish its undesirable effects. Many herbs and herbal supplements have been explored for their ef- fects in the management of Parkinson disease (Houghton and Howes, 2005; Li et al., 2004; Shults et al., 2002). The increasing evidence of impairment of mitochon- drial function, oxidative damage and inflammation in the pathogenesis of PD is emerging (Beal, 2003). One of the herbs that showed potential activities against all three factors is fenugreek (Trigonella foenum-graecum L., family Fabaceae), a commonly used spice worldwide. Fenugreek seeds has potent antioxidant (Anuradha and * Correspondence to: Dr. Prasad Arvind Thakurdesai, General Manager, Scientific affairs, Indus Biotech Private Limited, 1, Rahul Residency, Off Salunke Vihar Road, Kondhwa, Pune 411048, India. E-mail: prasad@indusbiotech.com PHYTOTHERAPY RESEARCH Phytother. Res. 28: 172–178 (2014) Published online 19 March 2013 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/ptr.4969 Copyright © 2013 John Wiley & Sons, Ltd. Received 14 August 2012 Revised 12 February 2013 Accepted 16 February 2013