28-day repeated dose oral toxicity of a herbal mixture dia-2, containing standardized extracts of allium sativum and lagerstroemia speciosa in sprague dawley rats.

Allium sativum [ASE] and Lagerstroemia speciosa [LSE] are widely used in folk medicine as a medication for diabetes. DIA-2 is a polyherbal antidiabetic formulation containing fixed combination [1:1 w/w] of standardized aqueous extracts of Allium sativum bulbs containing 1.1 % alliin w/w and 40 % hydroalcholic extract of Lagerstroemia speciosa leaves containing 1.28% w/w corosolic acid. Earlier studies in our laboratories have demonstrated the oral safety of DIA-2 on acute oral exposure to female Sprague Dawley [SD] rats and the antidiabetic activity of DIA-2 in high-fat diet fed/streptozotocin-induced diabetic rats. The ingredients of DIA-2 have long history safety but however, there is little toxicological information regarding the oral safety on repeated exposure of ASE and LSE when given as a combined mixture. The present study evaluated the repeated oral toxicity of DIA-2 in both the sexes of SD rats.  Rats were treated orally once with 62.5, 125, 250 mg/kg body weight, and animals were observed till the 28 days of study. On repeated oral administration, DIA-2 showed did not exhibit any clinical signs of toxicity, mortality, significant change in food, water consumption, body weight, mortality, clinical chemistry, hematology, organ weight, gross pathology and histopathology when varying doses of the DIA-2 were administered orally once daily for a period of 28 days. The NOAEL [No Observed Adverse Effect Level] of DIA-2 in this study was identified to be greater than 250 mg/kg/day. The results from the study suggest that there are no toxicologically significant effects on 28 day repeated oral administration of DIA-2 and the data also provide satisfactory preclinical evidence on its oral safety to support its use as a therapeutic agent in the treatment of diabetes mellitus

Introduction of Stereo Chemical Constraints into β -Amino Acid Residues

Over the last 20 years, a large body of work in the literature has focused on the folded structures formed by peptide sequences containing backbone homologated residues. Currently increasing interest in peptide based vaccines for several infectious diseases, and non-infectious diseases. The work of Seebach in Zurich [1] and Gellman in Madison [2], established that oligomers of β amino acid residues can form novel helical structures in solution and in the solid state. Two distinct types of hydrogen bonded helical structures were demonstrated in these studies for oligomeric β peptides. The C12 helix which is an analog of the canonical 310 helical structure in “all α” sequences, has the same hydrogen bond directionality (C=Oi …..H-Ni+3). The second helical form, the C14 helix, has the opposite directionality (C=Oi…..H-Ni+4), which is unprecedented in α peptide sequences [3,4]. These reports sparked a flurry of activity on the conformational properties of β peptide oligomers. An early study from Appavu et al. [3-7], had demonstrated that unsubstituted β and γ amino acid residues can be incorporated into oligopeptide helices, without disturbing the overall helical fold [4].</p

Design of Peptide Models for β-Hairpins and Equilibrating Helix-Hairpin Structures

It is well established that synthetic peptides containing a centrally positioned Type-I or Type-II β-turn can form well folded peptide hairpins (1). Earlier studies from this laboratory have established that D-Pro-Xxx segments nucleate β-hairpin structures, with formation of a central Type-II β-turn (2). The octapeptide (Boc-Leu-Phe-Val-Aib-D-Ala-Leu-Phe- Val-OMe) is a rare example of a synthetic peptide hairpin, containing a central Type-I β-turn. Hairpins with Type-I turns are considerably more twisted than their Type-II counterparts. The Aib-Xxx segment has also been shown to adopt a Type-I β-turn structure, resulting in incorporation into the centre of a long synthetic, helical peptide (3) (Figures 1,2).&nbsp;</p