Prevalence of chronic respiratory disorders in a rural area of North West India: A population-based study.

INTRODUCTION: Chronic respiratory diseases are an important cause of disability across the globe. The global burden of these diseases is showing a discernible upward trend. It is estimated that 500 million people suffer from them. MATERIALS AND METHODS: The study was conducted with the aim to estimate the prevalence of chronic obstructive pulmonary disease (COPD) in a rural Indian population. For this, a population-based survey was conducted using modified British Medical Research Council questionnaire. This was followed by subjecting the respondents to Wright's mini peak flow meter to find out the peak expiratory flow rate to diagnose the COPD cases. RESULTS: The prevalence of chronic bronchitis, bronchial asthma, and COPD was found to be 3.36%, 1.18%, and 4.21%, respectively. CONCLUSIONS: Chronic respiratory disorders are more prevalent among rural adults hinting to a rural-urban divide. Therefore, the focus of preventive strategies should take into account this difference.

Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities.

Inhibitors of drug metabolism have important implications in pharmaco-toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs.

Effects of piperine on enzyme activities and bioenergetic functions in isolated rat liver mitochondria and hepatocytes.

The influence of piperine on the enzymes and bioenergetic functions in isolated rat liver mitochondria and hepatocytes was studied. Piperine at lower concentrations (< 50 microM) did not affect the RCR and ADP:O ratios, state 4 and 3 respirations supported by site-specific substrates, viz. glutamate+malate, succinate, and ascorbate+TMPD. The site-specific effects became significantly apparent only at higher concentrations. Only the state 3 respiration supported by NAD-linked substrates was impaired equipotently in mitochondria and permeabilized hepatocytes; the effect appeared to be localized at energy-coupling site 1. In hypotonic treated mitochondria, respiration supported by three kinds of substrates was not affected. Among the respiratory chain-linked enzymes, the activity of NADH-dehydrogenase registered a significant decrease of about 25, 42, and 53% at 100, 150, and 180 microM piperine, respectively. The activity of Mg(++)-ATPase, however, was stimulated at concentrations above 150 microM. Among the matrix enzymes, only malate and succinate dehydrogenases were studied. Malate dehydrogenase only showed a strong concentration-related inhibition in both the forward and backward directions. Enzyme kinetics indicated noncompetitive inhibition with a very low Ki of 10 microM. The presence of unsaturated double bonds in the side chain of piperine appeared essential for producing this strong inhibition. The studies suggested that piperine produces concentration related site-specific effects on mitochondrial bioenergetics and enzymes of energy metabolism.

Impairment of UDP-glucose dehydrogenase and glucuronidation activities in liver and small intestine of rat and guinea pig in vitro by piperine.

The effects of piperine, a major ingredient of black pepper, on UDP-glucose dehydrogenase (UDP-GDH) and glucuronidation potentials of rat and guinea pig liver and intestine were studied. Piperine caused a concentration-related strong inhibition of UDP-GDH (50% at 10 microM) reversibly and equipotently, in both tissues. Partially purified rat liver UDP-GDH was used to obtain the kinetic values at pH optima of 9.4 and 8.6. At pH 9.4: KmUDP-glucose = 15 microM, Vmax = 5.2 nmol NADH/min/mg protein, Ki = 6 microM. With NAD, a Ki of 16 microM was obtained. At pH 8.6: Km = 35 microM, Vmax = 7.5 nmol, Ki = 15 microM. In all of these cases, piperine caused non-competitive inhibition. Data from structure-activity comparisons of piperine analogs indicated that the presence of conjugated double bonds in the side chain of the molecule is a factor in piperine inhibition. However, the UDP-glucuronic acid (UDPGA) contents were decreased less effectively by piperine in isolated rat hepatocytes compared with enterocytes of guinea pig small intestine. Piperine at 50 microM caused a marginal decrease of UDPGA in hepatocytes when the rate of glucuronidation of 3-hydroxybenzo[a]pyrene (3-OH-BP) decreased by about 40%. The decrease obtained at 10 microM piperine in intestinal cells was comparable to that obtained at 50-100 microM in hepatocytes. UDP-glucuronosyltransferase (UGT) activities towards 3-OH-BP (UGT1A1) and 4-OH-biphenyl (UGT2B1) were also determined. Piperine did not affect the rate of glucuronidation of 4-OH-biphenyl in rat liver, whereas that of 3-OH-BP was impaired significantly. In guinea pig small intestine, both these activities were inhibited significantly requiring less than 25 microM piperine to produce a more than 50% inhibition of UGT(s). The results suggested that (i) piperine is a potent inhibitor of UDP-GDH, (ii) inhibition is offered exclusively by the conjugated double bonds of the molecule, and (iii) piperine exerts stronger effects on intestinal glucuronidation than in rat liver.