Biotechnological interventions and genetic diversity assessment in Swertia sp.: a myriad source of valuable secondary metabolites.

The genus Swertia (Family: Gentianaceae) has cosmopolitan distribution which is present in almost all the continents except South America and Australia. Swertia genus has been renowned as one of the potent herbal drugs in the British, American, and Chinese Pharmacopeias as well as well-documented in the Indian traditional medicinal systems, viz. Ayurveda, Siddha, and Unani. Many species of this genus have therapeutic properties and have been used traditionally in the treatment of a number of health ailments viz. hepatitis, diabetes, inflammation, bacillary dysentery, cancer, malaria, fever etc. This genus is industrially important medicinal plant that has been used as a principal component in numerous marketed herbal/ polyherbal formulations. Medicinal usage of Swertia is endorsed to the miscellaneous compounds viz. xanthones, irridoids, seco-irridoids, and triterpenoids. A chain of systematic isolation of bio-active compounds and their diverse range of pharmacological effects during last 15-20 years proved this genus as industrially important plant. Due to the various practices of the Swertia species, annual demand is more than 100 tons per year for this important herb which is continuously increasing 10% annually. The market value rises 10% by the year as there is increased demand in national and international market resulted in adulteration of many Swertia spp. due to paucity of agricultural practices, exomorphological, phytochemical, and molecular characterization. Thus, efficient biotechnology methods are prerequisite for the mass production of authentic species, sustainable production of bio-active compounds and ex situ conservation. A chain of systematic biotechnological interventions in Swertia herb during last 20 years cover the assessment of genetic diversity, in vitro sustainable production of bio-active compounds and mass propagation of elite genotypes via direct and indirect organogenesis. This review attempts to present the comprehensive assessment on biotechnological process made in Swertia over the past few years. KEY POINTS: • Critical and updated assessment on biotechnological aspects of Swertia spp. • In vitro propagation and genetic diversity assessment in Swertia spp. • Biosynthesis and sustainable production of secondary metabolites in Swertia spp.

Optimization of salicylic acid and chitosan treatment for bitter secoiridoid and xanthone glycosides production in shoot cultures of Swertia paniculata using response surface methodology and artificial neural network.

BACKGROUND: In this study, response surface methodology (RSM) and artificial neural network (ANN) was used to construct the predicted models of linear, quadratic and interactive effects of two independent variables viz. salicylic acid (SA) and chitosan (CS) for the production of amarogentin (I), swertiamarin (II) and mangiferin (III) from shoot cultures of Swertia paniculata Wall. These compounds are the major therapeutic metabolites in the Swertia plant, which have significant role and demand in the pharmaceutical industries. RESULTS: Present study highlighted that different concentrations of SA and CS elicitors substantially influenced the % yield of (I), (II) and (III) compounds in the shoot culture established on modified ½ MS medium (supplemented with 2.22 mM each of BA and KN and 2.54 mM NAA). In RSM, different response variables with linear, quadratic and 2 way interaction model were computed with five-factor-three level full factorial CCD. In ANN modelling, 13 runs of CCD matrix was divided into 3 subsets, with approximate 8:1:1 ratios to train, validate and test. The optimal enhancement of (I) (0.435%), (II) (4.987%) and (III) (4.357%) production was achieved in 14 days treatment in shoot cultures of S. paniculata elicited by 9 mM and 12 mg L- 1 concentrations (SA) and (CS). CONCLUSIONS: In optimization study, (I) show 0.170-0.435%; (II) display 1.020-4.987% and (III) upto 2.550-4.357% disparity with varied range of SA (1-20 mM) and CS (1-20 mg L- 1). Overall, optimization of elicitors to promote secoiridoid and xanthone glycoside production with ANN modeling (r2 = 100%) offered more significant results as compared to RSM (r2 = 99.8%).

Chronomics of Circulating Plasma Lipid Peroxides and Antioxidant Enzymes in Renal Stone Formers.

The chronome of lipid peroxidation and anti-oxidant defense mechanisms may relate to the efficacy and management of time qualified preventive therapeutic and dietary interventions. One hundred renal stone patients, 20-60 years of age, and 50 clinically healthy volunteers, 21-45 years, were synchronized for 1 week with diurnal activity from 06:00 to 22:00 and nocturnal rest. All subjects took their usual meals three times daily (breakfast around 08:30, lunch around 13:00, and dinner around 20:30) with usual fluid intake. Drugs known to affect free radical system were not taken. Blood samples were collected at 6-h intervals for 24-h under standardized, presumably 24-h synchronized conditions. Determinations included plasma lipid peroxides, in terms of malondialdehyde (MDA) and blood superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT) activities. A marked circadian variation was demonstrated for each studied variable by population-mean cosinor in renal stone patients and healthy participants (p < 0.001). By comparison to healthy subjects, parameter tests indicate that the stone formers had a higher MESOR of MDA, but a lower MESOR of SOD, GPx, GR and CAT. Furthermore, the patients also differed from the healthy controls in terms of their circadian amplitude and acrophase (tested jointly) of all variables (p < 0.001). Mapping the broader time structure with multifrequency circadian characteristics of oxidants and anti-oxidants is needed for exploring their role as marker in the treatment and management of urolithiasis.

Linear Analysis of Autonomic Activity and Its Correlation with Creatine Kinase-MB in Overt Thyroid Dysfunctions.

Autonomic activity may be deranged in thyroid dysfunctions and may lead to cardiovascular morbidity and mortality. Myopathy is a common manifestation in thyroid disorders and may be associated with raised serum creatine kinase (CK). We hypothesized that cardiovascular abnormality in thyroid dysfunction may manifest as raised CK-MB. This study was designed to investigate the correlation of CK and its isoform CK-MB with thyroid profile and linear parameters of heart rate variability (HRV). The study was conducted on 35 hypothyroid and hyperthyroid patients each, and 25 age-matched healthy controls. Autonomic activity was assessed by simple short term 5-min HRV. Biochemical evaluation of serum thyroid profile, CK-NAC and CK-MB were estimated in all the subjects. Our results demonstrated low HRV in hypo- as well as hyperthyroid patients. We observed significantly higher serum CK levels in hypothyroid patients when compared to hyperthyroids and controls. However, no significant differences were observed in CK-MB levels in the three groups. Significant positive correlation of CK with TSH and negative correlation with some HRV parameters (LF power, HF power, total power, SDNN, RMSSD) was observed in hypothyroid patients. Whereas correlation of CK-MB with thyroid profile as well as HRV parameters was non-significant in all the groups. Based on the CK and CK-MB findings and their correlation, we conclude that the cardiovascular changes seen in thyroid dysfunctions may primarily be due to autonomic imbalance without apparent cardiac muscle involvement. Whereas, raised CK levels indicate predominantly skeletal muscle involvement in hypothyroid patients.

Erratum to: Linear Analysis of Autonomic Activity and Its Correlation with Creatine Kinase-MB in Overt Thyroid Dysfunctions.

[This corrects the article DOI: 10.1007/s12291-017-0659-0.].

Circadian Periodicity of Circulating Plasma Lipid Peroxides, Uric Acid and Ascorbic Acid in Renal Stone Formers.

Circadian periodicity of plasma lipid peroxides and serum ascorbic acid and uric acid levels were studied in one hundred renal stone formers (55 women and 45 men; age 20-60 years) and 50 clinically healthy volunteers (21 women and 29 men; age 21-45 years) with diurnal activity from 06:00 to 22:00 and nocturnal rest. A marked circadian variation was demonstrated by population-mean-cosinor for all studied variables in stone formers and healthy subjects. By comparison to the healthy controls, parameter tests indicate that the stone formers had a higher MESOR (±SE) of MDA (2.90 ± 0.03 vs. 2.28 ± 0.06; F = 94.929, p < 0.001), a lower MESOR of serum ascorbic acid (0.722 ± 0.010 vs. 0.839 ± 0.10; F = 32.083, p < 0.001), and a similar MESOR of serum uric acid. Furthermore, the patients also differed from the healthy subjects in terms of their circadian amplitude and acrophase (tested jointly) of all three variables (p < 0.001). The demonstration herein of a circadian rhythm in MDA, serum ascorbic and uric acid suggests that these variables could also serve as markers to optimize the timing of treatment and to assess the patient's response to treatment for further management.

Phenological documentation of an invasive species, Sapium sebiferum (L.) Roxb.

Phenological documentation and plant invasion are key contemporary issues in the biological sciences. Recognizing this, the present paper describes the phenological stages of an invasive species, Sapium sebiferum (L.) Roxb. A tree of the species was marked, and daily visits were made for recording its phenology. The Biologische Bundesanstalt, Bundessortenamt and CHemical industry (BBCH) scale was used for documenting the same. Of the total ten principal stages, eight were observed in the species. These stages started with bud development (stage 01) in the month of March and ended with leaf fall (stage 97) in the month of December. Descriptions of the phenological stages and their dates are provided in the text. It is hoped that such a phenological scale will be helpful in managing plant invasion.

Performance evaluation of bulk freeze dried starter cultures of dahi and yoghurt along with probiotic strains in standardized milk of cow and buffalo.

Performance of bulk freeze dried (BFD) cultures of dahi (D) and yoghurt (Y) either with or without probiotic cultures (AB -Lactobacillus acidophilus and Bifidobacterium bifidum) in standardized milk of cow and buffalo was evaluated. In buffalo milk, significantly (p < 0.05) low viable count of probiotic culture combination of dahi cultures (DAB) over non probiotic combination (D) was noticed; whereas, difference in counts of yoghurt culture combinations Y and YAB was not significant. The culture activity of D and DAB was similar in both types of milk, however, the volatile acidity (VA) produced by combination D was higher (32.5 ml/50 g sample) in buffalo milk than in cow milk (29.2 ml/50 g sample). Whereas, DAB produced very low amount of VA (16 ml/50 g sample) both in cow and buffalo milk. The diacetyl and tyrosine contents produced by either D or DAB in cow or buffalo milk were in the same order. Although Y and YAB produced slightly more VA in buffalo milk than in cow milk, significant change in the performance of yoghurt cultures (Y or YAB) both in cow and buffalo milk was not noticed. However, the VA and acetaldehyde produced by YAB either in cow and buffalo milk was higher than that by combination Y. Addition of probiotic cultures significantly enhanced the production of acetaldehyde content in both types of milk. Difference in tyrosine content in yoghurt made either with cow or buffalo milk was not significant. Overall, the present study indicated that the BFD cultures can be used to prepare dahi or yoghurt either from cow or buffalo milk, without affecting the biochemical profile of these products.

Cytological evaluation of Apiaceae Lindl. from Western Himalayas.

The present paper deals with cytological studies on 31 populations covering 17 species belonging to 10 genera of Apiaceae from Western Himalayas. The chromosome numbers in the two species as Chaerophyllum capnoides (n = 11) and Heracleum brunonis (n = 11), along with additional cytotypes for Pimpinella acuminata (n = 9) and Sium latijugum (n = 12) have been reported for the first time on world-wide basis. The genus Pleurospermum, although cytologically worked out earlier from outside India, its species densiflorum (n = 11) makes first representation of the genus from India. Besides, the chromosome number in Chaerophyllum aromaticum (n = 11) have been worked out for the first time from India. The course of meiosis varies from normal to abnormal in different populations of Chaerophyllum villosum, Pimpinella achilleifolia and Sium latijugum while abnormal meiotic course has been observed in all the studied populations of Chaerophyllum acuminatum, C. aromaticum, C. capnoides, Pimpinella acuminata, P. diversifolia, Pleurospermum densiflorum and Vicatia coniifolia. Such taxa are marked with meiotic abnormalities in the form of cytomixis, chromatin stickiness, formation of laggards and bridges resulting into abnormal microsporogenesis. The occurrence of structural heterozygosity has been recorded in the Chaerophyllum acuminatum and C. aromaticum. The effect of these abnormalities is clearly seen on the pollen size and fertility.

Alien flora of Indian Himalayan state of Himachal Pradesh.

Recognizing the array of effects that invasive alien species have, documenting their status from biodiversity rich regions has been much emphasized. Lack of such studies is a major limitation that hampers proper management of alien species. The present paper, therefore, documents the alien flora of the Indian Himalayan state of Himachal Pradesh (HP) based on data obtained from literature and herbarium records. The alien flora of HP comprises of 497 species belonging to 85 families. Majority of them belong to family Asteraceae (59 species), followed by Poaceae (47 species) and Fabaceae (43 species). Amongst the genera, Ipomoea (9 species), Eucalyptus and Euphorbia (7 species each) are the most predominant. Herbs constitute the majority (i.e., 73%) of alien species and a large percentage of them (i.e., 22.94%) have South America as their native region. Further, of the total alien species, 248 are intentional introductions and majority (31% species) have been introduced for ornamental purposes. It was revealed that 34% species have naturalized while 29% species have become invasive. Today, in addition to human-disturbed landscapes, alien species have also been reported from dense forests. Himalaya being a biodiversity hotspot and HP being a bio-rich Himalayan state, it is hoped that this inventory and assessment of alien flora will help in designing informed management and monitoring strategies against problematic plant invasions in the state.

Cytomorphological studies in some members of tribe Paniceae (Poaceae) from district Kangra of Himachal Pradesh (Western Himalayas).

The present paper deals with cytological studies on the population basis of 21 species belonging to 9 genera of tribe Paniceae of family Poaceae from cytologically unexplored area of Western Himalayas i.e. district Kangra of Himachal Pradesh for the assessment of genetic diversity of grass flora. On world-wide basis, the chromosome counts have been made for the first time for three species such as Brachiaria remota (n = 16), Digitaria granularis (n = 36) and Isachne albens (n = 5). Similarly, on India basis, altogether new records are made for two species such as Echinochloa cruspavonis (n = 27) and Paspalum distichum (2n = 50). A comparison of the different euploid cytotypes studied at present for Digitaria adscendens, D. setigera and Oplismenus compositus revealed significant variations in their morphology, depicting increase in some of the characters of polyploid cytotypes. The course of meiosis has been observed to be normal in all the studied populations with high pollen fertility except for two species such as Paspalum dilatatum and P. distichum marked with abnormal meiosis and reduced pollen fertility.

Cytological studies of Brassicaceae burn. (Cruciferae juss.) from Western Himalayas.

Cytological studies have been carried out on 12 species of Brassicaceae Burn. on population basis from different geographical areas of Kashmir and Himachal Pradesh in the Western Himalayas. Variable chromosome reports for Barbaraea intermedia (n = 16), Cardamine loxostemonoides (n = 8), Nasturtium officinale (n = 8), Sisymbrium orientale (n = 14) on world-wide basis have been added to the previous reports of these species. The chromosome numbers in seven species as Barbaraea intermedia (n = 8), B. vulgaris (n = 8), Capsella bursa-pastoris (n = 8), Descuriania sophia (n = 10), Rorippa islandica (n = 8), Sisymbrium strictum (n = 7) and Thlaspi alpestre (n = 7) have been worked out for the first time from India. The meiotic course in the populations of seven species such as Barbaraea intermedia, Capsella bursa-pastoris, Coronopus didymus, Descuriania sophia, Nasturtium officinale, Sisymbrium orientale and S. strictum varies from normal to abnormal while all the populations of two species Barbaraea vulgaris and Sisymbrium irio show abnormal meiotic course. Meiotic abnormalities are in the form of cytomixis, chromosomal stickiness, unoriented bivalents, inter-bivalent connections, formation of laggards and bridges, all resulting into abnormal microsporogenesis. Heterogenous sized fertile pollen grains and reduced reproductive potentialities have invariably been observed in all the meiotically abnormal populations. However, the meiotic course in all the populations of Cardamine loxostemonoides, Rorippa islandica and Thalspi alpestre is found to be normal with high pollen fertility.

Balsamin, a novel ribosome-inactivating protein from the seeds of Balsam apple Momordica balsamina.

Plant seeds, a rich source of proteins, are considered important for their application as functional ingredients in a food system. A novel ribosome-inactivating protein (RIP), balsamin was purified from the seeds of Balsam apple, Momordica balsamina. Balsamin was purified by ion exchange chromatography on CM Sepharose and gel filtration on superdex-75. It has a molecular weight of 28 kDa as shown by SDS-PAGE analysis. Balsamin inhibits protein synthesis in a rabbit reticulocyte lysate-based cell free translation assay with an IC(50) of 90.6 ng ml(-1). It has RNA N-glycosidase activity and releases a 400-base long fragment termed the Endo fragment from 28S rRNA in the same manner as does saporin-6 from Saponaria officinalis. The N-terminal sequence analysis of the first 12 amino acids of balsamin revealed that it shares 83% similarity with type I RIP α-MMC from Momordica charantia and 50% similarity with ß-MMC (from Momordica charantia), bryodin I (from Bryonia dioica) and luffin a (from Luffa cylindrica). Balsamin was further characterized by mass spectrometry. CD spectroscopic studies indicate that secondary structure of balsamin contains helix (23.5%), ß-strand (24.6%), turn (20%) and random coil (31.9%). Thus RIPs activity expressed in vegetables like Momordica sp. advocates its usage in diet.

Pyrido[1,2-a]pyrimidin-4-ones as antiplasmodial falcipain-2 inhibitors.

Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is a promising target for antimalarial chemotherapy and inhibition of this protease affects the growth of parasite adversely. A series of pyrido[1,2-a]pyrimidin-4-ones were synthesized and evaluated for their in vitro FP-2 inhibitory potential. Compounds (14,17) showed excellent FP-2 inhibition and can serve as lead compounds for further development of potent FP-2 inhibitors as potential antimalarial drugs.

Comparative therapeutic efficacy and safety of type-II collagen (UC-II), glucosamine and chondroitin in arthritic dogs: pain evaluation by ground force plate.

The investigation was conducted on client-owned moderately arthritic dogs with two objectives: (i) to evaluate therapeutic efficacy of type-II collagen (UC-II) alone or in combination with glucosamine hydrochloride (GLU) and chondroitin sulphate (CHO), and (ii) to determine their tolerability and safety. Dogs in four groups (n = 7-10), were treated daily for a period of 150 days with placebo (Group-I), 10 mg active UC-II (Group-II), 2000 mg GLU + 1600 mg CHO (Group-III), and UC-II + GLU + CHO (Group-IV). On a monthly basis, dogs were evaluated for observational pain (overall pain, pain upon limb manipulation, and pain after physical exertion) using different numeric scales. Pain level was also measured objectively using piezoelectric sensor-based GFP for peak vertical force and impulse area. Dogs were also examined every month for physical, hepatic (ALP, ALT and bilirubin) and renal (BUN and creatinine) functions. Based on observations, significant (p < 0.05) reduction in pain was noted in Group-II, III, and IV dogs. Using GFP, significant increases in peak vertical force (N/kg body wt) and impulse area (N s/kg body wt), indicative of a decrease in arthritis associated pain, were observed in Group-II dogs only. None of the dogs in any group showed changes in physical, hepatic or renal functions. In conclusion, based on GFP data, moderately arthritic dogs treated with UC-II (10 mg) showed a marked reduction in arthritic pain with maximum improvement by day 150. UC-II, GLU and CHO operate through different mechanisms of action, and were well tolerated over a period of 150 days.

Spectral analysis of heart rate variability in bronchial asthma patients.

The study was carried in the Departments of Physiology and Medicine at S.M.S. Medical College, Jaipur. Thirty patients of bronchial asthma, aged 20-30 years attending outpatient clinics of S.M.S. Hospital and thirty healthy volunteers were recruited in the present study for spectral analysis of Heart Rate Variability (HRV) using impedance peripheral pulse in the right forearm. Two spectral components were recorded namely high frequency (HF) component (0.15-0.4 Hz), an indicator of vagal efferent activity and low frequency (LF) component (0.04-0.15 Hz), replicator of composite sympatho-vagal interplay. These components were analyzed as LF nu (Low Frequency normalized unit), HF nu (High Frequency normalized unit) and LF/HF ratio. Low frequency component in absolute units of the asthmatic patients differed insignificantly (P > 0.05) from LF of the subjects, whereas the same calculated as normalized units was found to be significantly low in the patient group (P < 0.01), as compared to that of the control group. The High Frequency (in absolute units) index of HRV was significantly high in asthmatics (P < 0.01) as compared to the HF (absolute units) of controls. Similar trend was observed in the normalized units of HF (P<0.01). LF/HF ratio was not significantly different in patient and control groups (P > 0.05). It was concluded that a significantly raised central vagal outflow and a concomitant significantly low central sympathetic efferent could be appreciated in asymptomatic asthmatic patients as compared to that in the control group. This deranged sympathovagal interplay with parasympathetic dominance could be a plausible pathophysiological mechanism leading to airway obstruction, the hallmark of bronchial asthma.

Optimization of harvest and extraction factors by full factorial design for the improved yield of C-glucosyl xanthone mangiferin from Swertia chirata.

Swertia chirata Buch.-Ham. ex C.B. Clarke is an important medicinal plant used in various herbal formulations as it shows significant biological activities such as hepatoprotective, hypoglycemic, anti-inflammatory, antimalarial, antioxidant and anti-parkinson. C-glucosyl xanthone glycoside (mangiferin) is known as bio-marker compound of genus Swertia L. Development of efficient extraction methods of C-glucosyl xanthone mangiferin from Swertia chirata was attempted by optimizing the pre-harvest, post-harvest and extraction techniques by full factorial design. Firstly, a full factorial design was implemented to evaluate the single and interactive effects of pre-harvest (growth stage and plant part), post-harvest (drying condition and storage periods) followed by selection of best extraction technique such as heat reflux extraction (HRE), microwave assisted extraction (MAE) and ultrasound assistant extraction (UAE) at different solvent types on mangiferin yield. HPTLC and HPLC techniques were used for the determination of mangiferin content in extracts generated from different plant samples. In addition, anti-oxidant and anti-diabetic properties were determined by using DPPH assay and percentage inhibition of α­amylase enzyme. Substantial variation of mangiferin yield, ranged from 1.46 to 4.86% was observed, depending on the growth stage, plant part, drying condition, storage periods and extraction method. Results showed that drying of the leaves of Swertia chirata in the shade harvested at budding stage and stored for not more than 1 month was recommended for obtaining a higher mangiferin yield. Among different extraction techniques, MAE and UAE in 50% aqueous ethanol solvent were found to be efficient and cost-effective with better yield of mangiferin (4.82% and 4.86%, respectively) as compared to HRE (4.14%). Highest DPPH activity and percentage inhibition of α­amylase was observed in the aqueous ethanol extract of S. chirata leaves harvested at bud-stage of plant followed by flowering stage. The study shows that optimization of various factors by full factorial design was found to be an effective procedure to improve mangiferin yield from Swertia chirata and can be used for extraction of mangiferin.

Validation and quantification of major biomarkers in 'Mahasudarshan Churna'- an ayurvedic polyherbal formulation through high-performance thin-layer chromatography.

BACKGROUND: Mahasudarshan Churna (MC) is a polyherbal Ayurvedic medicine that is employed in fever (especially chronic type), cold and malaria, improvement of digestion and appetite, removes toxins from the blood, boosts immunity and protects against common bacterial infections. METHODS: Validation and quantification of oleanolic acid (OA), ursolic acid (UA), mangiferin (M), gallic acid (GA), quercetin (Q) and curcumin (C) in commercial MC formulations by HPTLC method. Mobile phase, hexane: ethyl acetate: acetone (16.4: 3.6: 0.2, v/v) was used for the separation of OA and UA; ethyl acetate: glacial acetic acid: formic acid: water (20: 2.2: 2.2: 5.2 v/v) for the development of M; and toluene: ethyl acetate: formic acid (13.5: 9: 0.6 v/v) for the separation of GA, Q and C in crude sample extracts. Visualization and scanning were performed at λ = 530 nm for OA and UA, at λ = 254 nm for M and at λ = 366 nm for GA, Q and C. In addition, HPLC-PDA analysis was used to confirm the HPTLC results. RESULTS: Major bio-active compounds in MC formulations were oleanolic acid (1.54-1.78%), mangiferin (1.38-1.52%) and gallic acid (1.01-1.15%); followed by ursolic acid (0.79-0.98%), curcumin (0.45-0.67%) and quercetin (0.22-0.34%). CONCLUSION: Analysis of bio-active compounds in the present study was performed using HPTLC methods and later HPTLC results were compared with HPLC. These two methods give comparable results and there was no statistically significant difference between the mean values for all extracts. Present study concluded that this HPTLC technique is low cost, fast, precise, and accurate which can be employed for the quantification of xanthonoid (M), triterpenoids (OA, UA) and phenolics (GA, Q and C) in samples/formulations. Furthermore, present HPTLC method can be conveniently employed for routine quality control analysis of all the six marker compounds in marketed Ayurvedic/herbal formulations.

Taurine in plasma and CSF: a study in healthy male volunteers.

In order to explore the interrelationship between plasma and cerebrospinal fluid taurine concentrations, three consecutive 6-ml fractions of cerebrospinal fluid were drawn from 30 healthy male volunteers in the early morning after 8 h in the fasting condition. Repeated plasma samples were drawn over 24 h the day before lumbar puncture. Taurine in plasma and cerebrospinal fluid was determined by high performance liquid chromatography. The subjects were categorized as extensive or poor metabolizers with respect to the cytochrome P450 2D6 genotype. The taurine cerebrospinal fluid/plasma ratio at 8 a.m. was negatively influenced by the plasma taurine concentration at 4 p.m. the previous day. It was also negatively influenced by body mass index and positively by the intraspinal pressure. Three poor metabolizers of cytochrome P450 2D6 had higher plasma taurine areas under the curve than 27 extensive metabolizers. Hypothetically, cytochrome P450 2D6 influences the transport of taurine across the blood-brain barrier.

Assessment of systemic interaction between Swertia chirata extract and its Bioactive constituents in rabbits.

The plant Swertia chirata (Gentianaceae) is known for its multifarious medicinal value in the Indian system of medicine (Ayurveda). Its methanol extracts having antidiabetic activity contains mangiferin, amarogentin, amaroswerin, sweroside and swertiamarin as active constituents. The pharmacokinetics of mangiferin and amarogentin have been carried out after intravenous administration of pure standards and extract from S. chirata (CT) in rabbits to assess systemic interaction. The remaining three components were also monitored in plasma for pharmacokinetic estimation based on the ratio analysis method. Mangiferin was characterized by a relative low clearance ( approximately 0.14 L/h/kg) and a lesser volume of distribution ( approximately 0.15 L/kg), while amarogentin exhibited a rapid clearance ( approximately 2.62 L/h/kg) and wide distribution ( approximately 1.08 L/kg) from the systemic circulation. No significant difference was observed in pharmacokinetic parameters of mangiferin and amarogentin either administered alone or as CT formulation in rabbits.