The complete chloroplast genome of the medicinally important plant Plumbago zeylanica L. (plumbaginaceae) and phylogenetic analysis.

Plumbago zeylanica L. 1753 is a medicinally-important herb in family Plumbaginaceae. In this study, we assembled and reported the complete chloroplast genome of P. zeylanica. The plastome of P. zeylanica was 169,178 bp, including a large single-copy region of 92,135 bp, a small single-copy region (SSC) of 13,455 bp and a pair of inverted repeat regions (IRs) of 31,794 bp. It contained 124 genes, including 79 protein-coding genes, 37 tRNA genes and eight rRNA genes. Phylogenetic analysis showed that P. zeylanica formed a close relationship with P. auriculata in Plumbago. The first complete chloroplast genome report of P. zeylanica providing an opportunity to explore the genetic diversity, and would be also helpful in the species identification and conservation.

TLC and HPLC methods for the determination of plumbagin for the diagnosis of poisoning by Plumbago scandens L.

Plumbago scandens L. (Plumbaginaceae) occurs in all regions of Brazil. It has been described as toxic to cattle and goats. Caustic lesions in the upper digestive tract characterize poisoning. P. scandens contains a naphthoquinone named plumbagin, which presents high cytotoxic activity. Plumbago auriculata Lam., a widely used ornamental plant, is considered potentially toxic, but there is limited data about its toxicity. This work aimed to validate analytical methodologies for determining the levels of plumbagin in samples of leaves, stems, and rumen content to be used as an auxiliary chemical marker in the laboratory diagnosis of intoxication. One methodology used thin layer chromatography (TLC), and another used high-performance liquid chromatography (HPLC). The presence of palisade grass (Urochloa brizantha (Hochst. ex A.Rich.) R.D.Webster), Guinea grass (Megathyrsus maximus (Jacq.) B.K.Simon & S.W.L.Jacobs), corn silage, and rumen content did not interfere with plumbagin in the two methodologies. The TLC methodology generates qualitative results but is simple to implement and has a low cost. The HPLC methodology showed a limit of detection (LOD) of 0.01 µg/mL and a limit of quantification (LOQ) of 0.05 µg/mL. Leaf and stem samples of P. scandens evaluated showed high levels of plumbagin (0.261 ± 0.087 % and 0.327 ± 0.055 %, respectively). In contrast, leaves of P. auriculata did not show detectable levels of the toxin, and some stem samples showed low levels (up to 0.000114 %). Thus, these methodologies can be used to confirm or rule out the consumption of P. scandens in rumen content from animals suspected of poisoning.

Purification and structural characterization of two polysaccharides with anti-inflammatory activities from Plumbago zeylanica L.

Plumbago zeylanica L., a traditional Chinese medicine, has anti-bacterial and anti-inflammatory effects, and it is critical important to explore the chemical compounds and evaluate their biological actions from the medicinal plant. However, the chemical structure and biological activities of polysaccharides from P. zeylanica. were still poorly understood. In this study, two water-soluble polysaccharides named WPZP-2-1 and WPZP-2-2 were purified from P. zeylanica L. Chemical and spectroscopic tests showed that the main chain of WPZP-2-1 was →4)-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→, and the branch chain was galactose or arabinose. The main chain of WPZP-2-2 was composed of →4)-α-D-GalpA-(1 â†’ 2)-α-L-Rhap-(1→, and the O-2 and O-3 of →4)-α-D-GalpA had a small amount of acetylation. In addition, in vitro test showed that WPZP-2-1 and WPZP-2-2 significantly improved the inflammatory damage of LPS + IFN-γ-induced THP-1 cells via reducing the protein levels of CD14, TLR4 and MyD88, thereby promoting IL-10 expression and inhibiting the mRNA levels of TNF-α and IL-1ß. Those findings indicated that WPZP-2-1 and WPZP-2-2 from the plant should be served as the potential anti-inflammatory agents.

Five undescribed guanidine alkaloids from Plumbago zeylanica.

Five undescribed guanidine alkaloids, plumbagines HK (1-4) and plumbagoside E (5), as well as five known analogues (6-10) were isolated from the roots of Plumbago zeylanica. Their structures were established by extensive spectroscopic analyses and chemical methods. In addition, 1-10 were accessed their anti-inflammatory activities by measuring nitric oxide (NO) concentrations in LPS-induced RAW 264.7 cells. However, all compounds especially 1 and 3-5 could not inhibit the secretion of NO but significant increase the secretion of NO. The result reminded us that 1-10 may become potential novel immune potentiators.

Comparative hepatoprotective activity of detoxified roots of Plumbago zeylanica L. and Plumbago rosea L. in Wistar rats.

BACKGROUND: Paracetamol (acetaminophen) toxicity is considered to be one of the major causes of drug-induced hepatic failure. Citraka (Plumbago rosea L. and Plumbago zeylanica L.) was mentioned in Ayurveda classics as a remedy in liver disorders. OBJECTIVE(S): The aim of the study was to experimentally evaluate the comparative effect of hepatoprotective activity of detoxified root decoction of the two species of Citraka against paracetamol-induced hepatotoxicity in male Wistar albino rats. MATERIALS AND METHODS: The hepatoprotective effect of Citraka decoction of two species was evaluated by the assessment of biochemical parameters such as SGOT, SGPT, alkaline phosphatase, total bilirubin, direct bilirubin, and serum creatinine. The study was also supported by histopathological assessment of liver sections. RESULTS: The results showed the elevated concentration of biochemical markers and histopathological degenerative changes in animals treated with paracetamol indicating severe hepatic damage; whereas, the treatment with decoction of both the species of Citraka showed significant reduction in the serum markers and regenerative changes in the histopathological specimens pointing towards its effectiveness as a hepatoprotective drug. CONCLUSION: The present study showed Citraka's effectiveness as a hepatoprotective drug and proved that the detoxified root decoction of P. rosea L. has a significant protective activity against paracetamol-induced hepatotoxicity than P. zeylanica L.

Interference of quorum sensing regulated bacterial virulence factors and biofilms by Plumbago zeylanica extract.

There has been tremendous spread of antimicrobial resistance globally, mainly due to the excessive and unnecessary use of antibiotics, making the situation alarming. This has created a need for the development of alternative strategies to selectively target the bacterial pathogenicity without exerting selection pressure for the development of antimicrobial resistance. Targeting quorum sensing (QS)-mediated virulence and biofilms by nontoxic natural products is gaining importance as new control strategy to combat the virulence and biofilms of pathogenic bacteria. In this study, the crude extract of Plumbago zeylanica was fractioned in different solvents using liquid-liquid partitioning to obtain the most bioactive fraction. The inhibitory effect of the bioactive extract of P. zeylanica on QS at sub-minimum inhibitory concentrations (MICs) was studied against Chromobacterium violaceum 12472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. Biofilm inhibition was studied using microtiter plate assay, scanning electron microscopy, and confocal laser scanning microscopy. Major phytocompounds detected were cinnamaldehyde dimethyl acetal, plumbagin, asarone, 4-chromanol, phthalic acid, palmitic acid, ergost-5-en-3-ol, stigmasterol, and ß-sitosterol. The violacein production in C. violaceum 12472 was reduced by >80% in the presence of P. zeylanica hexane fraction (PZHF; 200 µg/ml). The most active PZHF inhibited QS-mediated virulence factors of P. aeruginosa PAO1 such as pyocyanin, pyoverdin, rhamnolipid production, motility, etc., significantly at sub-MICs. Similarly, PZHF showed 59 to 76% inhibition of biofilm formation of above test pathogens. The findings revealed that active fraction of P. zeylanica was effective against the QS-regulated functions and biofilms development of Gram -ve pathogenic bacteria.

Biocidal chitosan-magnesium oxide nanoparticles via a green precipitation process.

In the present scenario, the development of eco-friendly multifunctional biocidal substances with low cost and high efficiency, has become the center of focus. This study is, focused on the synthesis of magnesium oxide (MgO) and chitosan-modified magnesium oxide (CMgO) nanoparticles (NPs), via a green precipitation process. In this process, leaves extract of Plumbago zeylanica L was, used as a nucleating agent. The MgO and CMgO NPs exhibit face-centered cubic structures, as confirmed by XRD studies. Morphologically, the FESEM and TEM images showed that the MgO and CMgO NPs were spherical, with an average particle size of ~40±2 and ~37±2 nm, respectively. EDX spectra were used to identify the elemental compositions of the nanoparticles. By using FTIR spectra, the Mg-O stretching frequency of MgO and CMgO NPs were observed at 431 and 435 cm-1, respectively. The photoluminescence (PL) spectra of MgO and CMgO NPs, revealed oxygen vacancies at 499 nm and 519 nm, respectively, due to the active radicals generated, which were responsible for their biocidal activities. The toxicity effects of the nanoparticles developed, on cell viability (antibacterial and anticancer), were measured on the MCF-7 cell line and six different types of gram-negative bacteria. The antibacterial activities of the nanoparticles on: Klebsiella pneumoniae, Escherichia coli, Shigella dysenteriae, Pseudomonas aeruginosa, Proteus vulgaris and Vibrio cholerae bacteria, were studied with the well diffusion method. The MgO and CMgO NPs were tested on breast cancer cell line (MCF-7) via an MTT assay and it proved that CMgO NPs possess higher anticancer properties than MgO NPs. Overall, CMgO NPs showed a higher amount of cytotoxicity for both the bacterial and cancer cells when compared to the MgO NPs. Toxicity studies of fibroblast L929 cells revealed that the CMgO NPs were less harmful to the healthy cells when compared to the MgO NPs. These results suggest that biopolymer chitosan-modified MgO NPs can be used for healthcare industrial applications in order to improve human health conditions.

Molecular cloning and characterization of type III polyketide synthase from Plumbago zeylanica.

Two cDNAs encoding type Ш polyketide synthase (PKS1) and chalcone synthase (CHS, PKS2), were cloned from fresh leaves of Plumbago zeylanica L. (P. zeylanica). Their heterologous expression revealed that PKS1 catalyzed the formation of five α-pyrones from three to six acetate units by accepting acetyl-CoA and malonyl-CoA. In contrast, PKS2 catalyzed the formation of naringenin and bisnoryangonin by accepting p-coumaroyl-CoA and malonyl-CoA. Naringenin is thought to be involved in the biosynthesis of various bioactive flavonoids. PKS2 can be used to molecular breeding to enhance the production of these useful secondary metabolites via its overexpression.[Formula: see text].

De novo transcriptome analysis unravels tissue-specific expression of candidate genes involved in major secondary metabolite biosynthetic pathways of Plumbago zeylanica: implication for pharmacological potential.

KEY MESSAGE: The present study provides comparative transcriptome analysis, besides identifying functional secondary metabolite genes of Plumbago zeylanica with pharmacological potential for future functional genomics, and metabolomic engineering of secondary metabolites from this plant towards diversified biomedical applications. ABSTRACT: Plumbago zeylanica is a widely used medicinal plant of the traditional Indian system of medicine with wide pharmacological potential to treat several disorders. The present study aimed to carry out comparative transcriptome analysis in leaf and root tissue of P. zeylanica using Illumina paired end sequencing to identify tissue-specific functional genes involved in the biosynthesis of secondary metabolites, contributing to its therapeutic efficacy. De novo sequencing assembly resulted in the identification of 62,321 "Unigenes" transcripts with an average size of 1325 bp. Functional annotation using BLAST2GO resulted in the identification of 50,301 annotated transcripts (80.71%) and GO assigned to 18,814 transcripts. KEGG pathway annotation of the "Unigenes" revealed that 2465 transcripts could be assigned to 242 KEGG pathway maps wherein the number of transcripts involved in secondary metabolism was distinct in root and leaf transcriptome. Among the secondary metabolite biosynthesis pathways, the cluster of "Unigenes" encoding enzymes of 'Phenylpropanoid biosynthesis pathway' represents the largest group (84 transcripts) followed by 'Terpenoid Backbone biosynthesis' (48 transcripts). The transcript levels of the candidate unigenes encoding key enzymes of phenylpropanoid (PAL, TAL) and flavanoid biosynthesis (CHS, ANS, FLS) pathways were up-regulated in root, while the expression levels of candidate "Unigenes" transcript for monoterpenoid (DXS, ISPF), diterpenoid biosynthesis (SPS, SDS) and indole alkaloid pathways (STR) were significantly higher in leaf of P. zeylanica. Interestingly, validation of differential gene expression profile by qRT-PCR also confirmed that candidate "Unigenes" enzymes of phenylpropanoid and flavonoid biosynthesis were highly expressed in the root, while the key regulatory enzymes of terpenoid and indole alkaloid compounds were up-regulated in the leaf, suggesting that (differences in) the levels of these functional genes could be attributed to the (differential) pharmacological activity (between root and leaf) in tissues of P. zeylanica.

Standard operating procedure of Purification of Chitraka (Plumbago zeylanica Linn.) along with pharmacognostical and analytical profiles of Plumbagin.

INTRODUCTION: Shodhana (purification) is the process by which one can remove the impurity or toxicity of the raw drug and make the drug suitable for therapeutic purpose. Chitraka (Plumbago zeylanica Linn.) is well known drug in Ayurveda and root of this plant is being used for therapeutic purpose and requires purification before used as a medicine. AIMS AND OBJECTIVE: There is no data available for pharmacognostical and analytical profile of processed Chitraka, hence it was planned to develop SOP of processed Chitraka for its identity, purity and strength through pharmacognostical and analytical profile. MATERIALS AND METHODS: Chitraka roots were procured from Pharmacy, Gujarat Ayurved University, Jamnagar. Purification was done in five batches with Churnodaka (lime water). Organoleptic characters, microscopic features, pH, loss on drying, ash value, water soluble extracts, methanol soluble extracts and plumbagin quantification through high-performance thin layer chromatography (HPTLC) were carried out, before and after the purification. RESULTS: Average 98.07% yield of Chitraka was obtained after purification. Differences were found in the processed samples of Chitraka in organoleptic features, pharmacognostical characters and physicochemical parameters, which show the impact of purification procedure on Chitraka. In HPTLC profile, plumbagin content was 0.29% in unpurified Chitraka powder, where in it was noted 0.98% after purification. CONCLUSION: Increase in plumbagin content through pharmaceutical process of Chitraka purification with lime water indicates that, this operating procedure is simple, convenient and can be considered as standard procedure. The organoleptic features, pharmacognostical characters, values of physicochemical parameters and quantity of plumbagin of purified Chitraka powder may be utilized for quality assurance in future studies.

Fungal endophytes of Plumbago zeylanica L. enhances plumbagin content.

BACKGROUND: Plumbagin is one of the pharmaceutically important biomolecule with anticancer potential. Among the plants reported to produce plumbagin, P. zeylanica topped the list. The plumbagin production is very slow with low yield and maximum 0.5% (of dry weight) was reported in P. zeylanica. To meet the increasing demand of the plumbagin at global level, the P. zeylanica are exploited at commercial level, which may pose serious threat on the germplasm of the plant populations. So, it is needed to enhance the contents of plumbagin in P. zeylanica using biotechnological approaches. Among the various methods used to enhance the contents of plumbagin in P. zeylanica, utilization of fungal endophytes to enhance the plumbagin contents is a widely accepted approach. As fungal endophytes have the potential to synthesize various secondary metabolites and also reported to influence the synthesis of the secondary metabolites in plants. In the present study, an attempt was made to assess the effect of fungal endophytes of the Plumbago zeylanica L. on enhancement of plumbagin contents at in vivo level. RESULTS: Total 3 fungal endophytes were recorded from the roots of P. zeylanica collected from Khadki, Pune. The fungal endophytes were identified at morphological and molecular level. After 1 year of the treatment with fungal endophytes, significant enhancement of plumbagin was recorded in the roots of the P. zeylanica. Plumbagin contents in each were quantified against the standard plumbagin by employing LCMS-MS technique. Among the three fungal endophytes, the maximum enhancement of plumbagin content (122.67%) was reported with the treatment of Alternaria   sp. (Isolate-3) in the roots of the P. zeylanica compared to control. CONCLUSION: Among the three fungal endophytes, the maximum enhancement of plumbagin content (122.67%) was reported with Alternaria sp. (Isolate 3) in the roots of the pot-grown plants of P. zeylanica at in vivo level.

Phenolic constituents of Pumbago zeylanica and their anti-oxidative effects / 中草药

Objective: To investigate the phenolic compounds from Plumbago zeylanica and their anti-oxidant activities. Methods :The phenolic compounds and their analogues were isolated and purified by silica gel column chromatography, semi-preparative HPLC, and HPLC. Their structures were identified by spectroscopy data. The isolated compounds were tested for anti-oxidant activity by ABTS assay. Results: Twelve phenolic compounds were obtained and identified as (±)-5,5’-dimethoxyl ariciresionl 4’-O-β-D-glucopyranoside (1), tracheloside (2), quercetin-3-O-β-D-galactoside (3), quercetin-3-O-β-D-glucopyranoside (4), quercetin (5), quercetin 3-O-α-L-rhamnoside (6), kaempferol-3-O-α-L-rhamnoside (7), apigenin-6-C-β-D-glucopyranoside (8), luteolin 6-C-β- glucopyranoside (9), polybotrin (10), 3-O-(β-D-glucopyranosyl)-1-(3’,5’-dimethoxy-4’-hydroxyphenyl)-1-propanone (11), and (2E,4E,1’R,3’S,5’R,8’S)-dihydrophaseic acid-3’-O-β-D-glucopyranoside (12). The anti-oxidant activity experiment showed that compounds 3-9 displayed significant anti-oxidative activities. Conclusion: All of the twelve phenolic compounds are isolated from this plant for the first time. The isolated flavones 3-9 displayed significant anti-oxidative activities.

Purification and Characterization of an Active Principle, Lawsone, Responsible for the Plasmid Curing Activity of Plumbago zeylanica Root Extracts.

Plasmid curing is the process of obviating the plasmid encoded functions such as antibiotic resistance, virulence, degradation of aromatic compounds, etc. in bacteria. Several plasmid curing agents have been reported in literature, however, no plasmid curing agent can eliminate all plasmids from different hosts. Hence, there is always a need for novel plasmid curing agents that can be effectively used for reversal of plasmid encoded functions such as virulence, antibiotic resistance, etc. In the present study, an active principle responsible for the plasmid curing activity was purified from roots of Plumbago zeylanica by bioassay guided fractionation and identified as 2-hydroxy-1,4-naphthoquinone (lawsone), on the basis of spectral and analytical data such as NMR, GCMS, FTIR. Plasmid curing activity of lawsone was observed against reference as well as wild plasmids (pBR322, pRK2013, R136, pUPI281, and pUPI282) residing in a range of hosts. Curing of plasmid was confirmed by agarose gel electrophoresis. MICs of antibiotics against A. baumannii A24 (pUPI281) and E. coli (pRK2013) decreased significantly in presence of lawsone suggesting synergy between lawsone and antibiotics. Lawsone also inhibited transfer of plasmid pRK2013 to E. coli either by transformation or conjugation. Viability assays (MTT) revealed that lawsone was not toxic to mammalian cells. Thus, the present investigation has revealed lawsone as an effective plasmid curing agent capable of suppressing development and spread of antibiotic resistance. Further, lawsone has important application in basic research to identify phenotypes encoded by the plasmids in plasmid curing experiments. To the best of our knowledge this is the first report of plasmid curing activity of lawsone isolated from roots of P. zeylanica.

Anti-cell proliferation effect of naphthoquinone dimers isolated from Plumbago zeylanica.

Study of the chemical constituents of the roots of Plumbago zeylanica L. collected in Taiwan led to the isolation and identification of a new naphthoquinone dimer, plumzeylanone (1), along with eight known compounds (2-9). Nine naphthoquinones isolated from this plant were assayed for cell growth inhibition activity using NALM-6 (human B cell precursor leukaemia), A549 (human lung adenocarcinoma), Colo205 (human colorectal adenocarcinoma) and KB (human epidermoid carcinoma). Plumzeylanone (1), a novel plumbagin dimer, suppressed cell proliferation in only NALM-6 cells (IC50 3.98 µM). However, maritinone (9) showed strong inhibition of cell growth in all cell lines tested (0.12 < IC50 < 9.06 µM). This compound appeared to affect the cell cycle.

Methanolic Extract of Plumbago Zeylanica - A Remarkable Antibacterial Agent Against Many Human and Agricultural Pathogens.

OBJECTIVES: The current investigation was carried out to determine the cytotoxic and the antimicrobial activities of methanolic extracts of Plumbago zeylanica. METHODS: The stems, leaves, and whole plants were air dried and extracted with methanol by using a Soxhlet extractor for 72 hours at 55 - 60°C. The antimicrobial activities were determined from the zones of inhibition, which were measured by using the agar well diffusion method, and the cytotoxicity assays were performed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. RESULTS: The methanolic extracts of the stem and the leaves of Plumbago zeylanica were tested against six bacterial species and nine fungal species, and both extracts showed antimicrobial activity in a dose-dependent manner. The leaf extract of Plumbago zeylanica showed maximum antimicrobial activity against both Staphylococcus aureus sub sp aureus and Fusarium oxysporum. The stem extract was found to be more antimicrobial against the Pseudomonas aeruginosa and the Penicillium expansum species. MTT assays were used to test the cytotoxicity of the whole plant extract in the HCT-116 and the K-562 cell lines, and that extract was shown to have weak cytotoxicity in both cell lines. CONCLUSION: In the present study, the methanolic stem extracts of Plumbago zeylanica were found to possess remarkable antibacterial activities against many human and agricultural pathogens. The extracts were also found to possess significant antifungal activities, but the antifungal activities were less than the antibacterial activities. Finally, the extracts were found to have weak cytotoxicities in the HCT-116 and the K-562 cell lines.

Population structure and genetic diversity of the perennial medicinal shrub Plumbago.

Knowledge of the natural genetic variation and structure in a species is important for developing appropriate conservation strategies. As genetic diversity analysis among and within populations of Plumbago zeylanica remains unknown, we aimed (i) to examine the patterns and levels of morphological and genetic variability within/among populations and ascertain whether these variations are dependent on geographical conditions; and (ii) to evaluate genetic differentiation and population structure within the species. A total of 130 individuals from 13 populations of P. zeylanica were collected, covering the entire distribution area of species across India. The genetic structure and variation within and among populations were evaluated using inter-simple sequence repeat (ISSR) and randomly amplified DNA polymorphism (RAPD) markers. High levels of genetic diversity and significantly high genetic differentiation were revealed by both the markers among all studied populations. High values of among-population genetic diversity were found, which accounted for 60 % of the total genetic variance. The estimators of genetic diversity were higher in northern and eastern populations than in southern and western populations indicating the possible loss of genetic diversity during the spread of this species to Southern India. Bayesian analysis, unweighted pair group method with arithmetic average cluster analysis and principal coordinates analysis all showed similar results. A significant isolation-by-distance pattern was revealed in P. zeylanica by ISSR (r = 0.413, P = 0.05) and RAPD (r = 0.279, P = 0.05) analysis. The results obtained suggest an urgent need for conservation of existing natural populations along with extensive domestication of this species for commercial purpose.

Comparative toxicity profiles of Plumbago zeylanica L. root petroleum ether, acetone and hydroalcoholic extracts in Wistar rats.

INTRODUCTION: The root of Plumbago zeylanica Linn. is used in traditional medicine for the treatment of chronic inflammatory diseases and various disorders. The toxicity of this plant has not yet been extensively evaluated. AIM: To evaluate and compare the toxicity of P. zeylanica root petroleum ether (PZPE), acetone (PZAC), and the hydroalcoholic (PZHY) extracts. MATERIALS AND METHODS: The acute and sub-acute toxicities of extracts were evaluated according to OECD guidelines 425 and 407, respectively in female rats. RESULTS: PZPE was more toxic than PZAC and PZHA, based on LD50 values of 93.45, 928.4, and 928.4 mg/kg, respectively. This potency difference directly correlates with the plumbagin content of extracts. With regard to sub-acute toxicity, a significant increase in organ weights (liver, adrenal glands, and/or heart) was observed in PZPE and PZAC treated groups. All extracts produced a significant increase in serum aspartate aminotransferase and urea, and PZAC produced a significant increase in serum creatinine as compared to control. A decrease in hematocrit was observed in the highest dose PZPE group, and a decrease in leukocytes was observed in all PZAC groups. Hepatic and renal changes were observed in all extract treated groups. CONCLUSION: The findings of our study, thus demonstrate that liver and kidney are the primary organs being adversely affected following sub-acute administration of P. zeylanica root extract in rats.

Toxicogenomics of Phenylhydrazine Induced Hematotoxicity and its Attenuation by Plumbagin from Plumbago zeylanica.

BACKGROUND: High regenerative and proliferative capacity of blood and its components renders it to be at higher risk of adverse drug reactions (ADRs) which are manifested in several treatment regimens against various ailments such as cancers, viral diseases, and several metabolic disorders. OBJECTIVE: It is prudent to come up with some therapeutic entity that can prevent this damage and protects the blood from these ADRs. MATERIALS AND METHODS: We examined protective effects of Plumbago zeylanica (PZ) and its active constituent plumbagin (PL) on Sprague Dawley (SD) rats using a phenylhydrazine (Phz) induced hematotoxicity model. Hemoglobin (Hgb), red blood cells (RBCs), mean corpuscular volume, mean corpuscular Hgb (MCH), MCH concentration (MCHC), leukocytes and platelets were studied. Anti-oxidant enzymes superoxide dismutases 2 and 3 (SODs) and nuclear erythroid 2 p45-related factor 1 and 2 (Nfer-1 and 2) were also studied using quantitative real-time polymerase chain reaction (PCR). RESULTS: In Phz treated rats, the positive hematotoxic response was obtained in terms of deviated endpoints of blood indices. In PLtreated groups protective response was obtained in terms of normal endpoints of blood indices. In PCR studies, we observed the similar trend. Thus, it can be postulated that PL exerts its protective effects via modulation of anti-oxidant enzymes. CONCLUSION: The study proves that PL can be employed against combatting the ADRs associated with several therapeutic treatment regimens. Similar studies employing such pharmacological entities and their combinations may further prove to be effective against ADRs, especially in the context of blood cells. SUMMARY: Hematotoxicity is generally encountered in various therapeutic regimens as ADRs (Adverse Drug Reactions). Plumbagin, an active constituent of plant Plumbago zeylanica is tested for its anti-hematotoxic potential in Phenylhydrazine induced hematotoxicity model in Sprague dawley rats. In vivo, in-vitro and molecular studies confirmed the peremptory actions of PL. It was revealed in our studies that the anti-hematotoxic actions of Plumbagin are due to its capacity to modulate anti-oxidant enzyme system.

Effect of hydro-alcoholic root extract of Plumbago zeylanica l alone and its combination with aqueous leaf extract of Camellia sinensis on haloperidol induced parkinsonism in wistar rats.

BACKGROUND: Herbal medicines have been used to treat PD in ancient medical systems in Asian countries such as India, China, Japan and Korea based on their own anecdotal or experience-based theories. Mucuna pruriens commonly known asvelvet beans, or cow itch, are used in case of spasms associated with Parkinsonism. PURPOSE: To investigate the antiparkinsonism activity of hydro alcoholic root extract of P. zeylanica L (PZE) aloneand its combination withaqueous extract of C. sinensis leaves (AECS) in Haloperidol induced model. METHODS: Parkinsonism (PD) was induced by intraperitoneal administration of Haloperidol (1 mg/kg). The extracts/drugs being tested were administered orally (p.o) 60 min prior to the administration of the Haloperidol. Catalepsy was measured using the metal bar test. RESULTS: Haloperidol induced a time dependent increase in cataleptic score in rats, as compared to vehicle treated groups. All the groups ie L-dopa + carbidopa (syndopa), hydro-alcoholic extract of P. zeylanica alone and its combination with C. sinensis showed significantly (P<0.001) lower scores of catalepsy at all time periods as compared to Haloperidol. Results were analyzed by one way ANOVA followed by Dunnet's multiple comparison tests. CONCLUSION: It is concluded that P. zeylanica alone and its combination with C. sinensis exert a protective effect against PD, while bi-herbal extracts showed more significant protective effect. Hence it may offer a safer therapeutic approach to the treatment of PD and drug induced dyskinesia.

Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives.

A series of novel naphthoquinone amide derivatives of the bioactive quinones, plumbagin, juglone, menadione and lawsone, with various amino acids were synthesized. The compounds were characterized by (1)H NMR, (13)C NMR, Mass, IR and elemental analysis. All the compounds were evaluated for their anticancer activity against HeLa and SAS cancer cell lines and 3D-QSAR indicated the presence of electron donating group near sulphur enhanced the activity against HeLa cells. Among the derivatives synthesized, compounds 11f, 10a, 10b and 10g were the most active with IC50 values of 16, 12, 14 and 24.5 µM, respectively. The analogues were also screened for antimicrobial activity against two human bacterial pathogens, the Gram-positive Methicillin resistant Staphylococcus aureus (MRSA) and the Gram-negative Pseudomonas aeruginosa and a human yeast pathogen, Fluconazole resistant Candida albicans (FRCA). Among the synthesized compounds, 8g, 10g and 11g exhibited maximum antibacterial activity towards MRSA and antifungal activity against FRCA in well diffusion method.