Nitrosamine Impurities in Herbal Formulations: A Review of Risks and Mitigation Strategies.

Nitrosamines are a class of chemical compounds that have been found to be impurities in a variety of pharmaceutical products. These impurities have raised concerns due to their potential carcinogenic effects. Recent studies have identified nitrosamines as impurities in a number of pharmaceutical products including angiotensin II receptor blockers (ARBs) and proton pump inhibitors (PPIs). The presence of nitrosamines in these products has led to recalls and market withdrawals. In addition to pharmaceuticals, nitrosamines have also been found in some herbal medicines particularly those containing traditional Chinese medicinal ingredients. The presence of nitrosamines in herbal formulations poses a significant risk to public health and highlights the need for quality control and regulations in the herbal drug industry. The present review article aims to discuss nitrosamine impurities (NMI) prominent causes, risks and scientific strategies for preventing NMI in herbal formulations. The primary objective of this study is to examine the origins of nitrosamine contamination in herbal formulations, the risks associated with these contaminants, and the methods for reducing them. The significance of thorough testing and examination before releasing herbal products to the public is also emphasized. In conclusion, the presence of nitrosamines is not limited to pharmaceutical products and poses a significant threat to the safety of herbal drugs as well. Adequate testing and extensive research are crucial for producing and distributing herbal medicines to the general population.

A new pyrimidine alkaloid from the roots of Tadehagi triquetrum (L.) H.Ohashi.

Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae) is the most important plant in the herbal remedies. The present study focus on the isolation, in-silico and in-vitro studies of the two alkaloids C1 (5-(4-[(methylcarbamoyl) amino]-2-oxopyrimidin-1(2H)-yl) tetrahydrofuran-2-yl) methyl methyl carbamate is novel alkaloid and C2 13-Docosenamide is a known alkaloid. The chemical structures of compounds have been elucidated based on comprehensive techniques like GCMS, IR and NMR. In order to know the molecular mechanisms for the two compounds, in silico molecular docking study has been performed. Both compounds have shown perfect binding affinity to the enzymes TNF α, IL-4, IL-13 and 5 LOX Enzyme. The compounds also exhibited comparable G-scores and Glide energy values in comparison with the standard dexamethasone. In addition both the compounds have been tested for in vitro antioxidant assay by using ABTS and DPPH method and the results were compared with standard ascorbic acid.

Isolation and characterization of flavonoids from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi.

Three flavonoid compounds were isolated from the roots of medicinal plant Tadehagi triquetrum (L.) H.Ohashi, also known as Desmodium triquetrum (Fabaceae). On the basis of the chemical and spectral analysis, the compounds were identified as baicalein (Flavone), naringin and neohesperidin (Flavonone). To the best of our knowledge and based on the literature survey all three compounds were first time reported from this medicinal plant.[Formula: see text].

Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect.

BACKGROUND: Isolation of methyl gamma linolenate from Spirulina platensis using flash chromatography and its apoptosis inducing effect against human lung carcinoma A- 549 cell lines. METHODS: Gamma linolenic acid is an important omega-6 polyunsaturated fatty acid (PUFA) of medicinal interest was isolated from microalgae Spirulina platensis using flash chromatography system (Isolera system) as its methyl ester. The isolated methyl gamma linolenate was characterized by IR, (1)H NMR, (13)C NMR and mass spectral analysis and the data were consistent with the structure. RESULTS: The percentage yield of isolated methyl gamma linolenate is found to be 71% w/w, which is a very good yield in comparison to other conventional methods. It was subjected to in-vitro cytotoxic screening on A-549 lung cancer cell lines using SRB assay and result was compared with standard rutin. CONCLUSION: It may be concluded that the Flash chromatography system plays a major role in improving the yield for the isolation of methyl gamma linoleate from Spirulina platensis and the isolated molecule is a potent cytotoxic agent towards human lung carcinoma cell lines, however it may be further taken up for an extensive study.

Anticancer activity of cissampelos pareira against dalton's lymphoma ascites bearing mice.

BACKGROUND: Cissampelos pareira (Menispermaceae) is used in folk Indian system of alternative medicine, for its analgesic, antipyretic, diuretic, antilithic, and emmenagogue properties. OBJECTIVE: To evaluate Cissampelos pareira (C. pareira) for in vitro cytotoxicity and in vivo antitumor activity against Dalton's Lymphoma Ascites (DLA) cells in Swiss mice. MATERIALS AND METHODS: Cissampelos pareira was successively extracted using different solvents. In vitro cytotoxicity was assessed by the MTT assay. An in vivo study was carried out in methanol extract. Twenty-four hours after intraperitoneal inoculation of the DLA cells in mice, the methanol extract of C. pariera (MECP) was administered at 200 and 400 mg/kg body weight for 14 consecutive days. On day 14, six mice were sacrificed and the rest were kept alive for assessment of increase in life-span. The antitumor effect was assessed by evaluating the packed cell volume, viable tumor cell count, increase in body weight, and increase in life-span. The hematological and serum biochemical parameters and anti-oxidant properties were assessed by estimating the superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation. RESULTS: Methanol Extract of Cissampelos pariera (MECP) showed a potent cytotoxic activity, with an IC50 value of 95.5 µg/ml and a significant (P < 0.001) decrease in packed cell volume, viable cell count, and an increased lifespan (54 and 72%). The hematological and serum biochemical profiles were restored to normal levels in MECP-treated mice. The MECP-treated group significantly (P < 0.001) decreased SOD, lipid peroxidation, and CAT to normal. CONCLUSION: This study demonstrated that C. pariera exhibited significant in vitro and in vivo anti-tumor activities and that it was reasonably imputable to its increasing endogenous mechanism of antioxidant property.

Hydnocarpus: an ethnopharmacological, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hydnocarpus (Flacourtiaceae) includes forty species that are spread across the globe. In the Indian System of Medicine, Hydnocarpus pentandrus (Buch.-Ham.) Oken. is primarily used for treating leprosy and other skin disorders. It is known as "Chaulmoogra" and is also used to treat other indications including constipation, inflammation, blood disorders, and worm infestations. Various species of Hydnocarpus are also used in traditional medicine in China, Thailand, Malaysia, and Myanmar for several skin disorders. To assess the therapeutic potential of species from the Hydnocarpus genus and to determine future avenues for research. METHODS: All relevant scientific literature published up to the end of December 2013 was retrieved via a library and electronic search (SciFinder, PubMed, ScienceDirect, and Google Scholar). Manual searches of traditional books like to ancient classics, including Vaidya Yoga Ratnavali, Siddha Materia Medica, and contemporary references including The Ayurvedic Pharmacopoeia of India and The Ayurveda Formulary, were also performed. RESULTS: Seed oil from species of the Hydnocarpus genus is used for medicinal purposes, predominantly for various skin disorders. This oil is reported to contain a characteristic class of compounds known as cyclopentenyl fatty acids. Furthermore, seeds of this genus are reported to contain triglycerides of fatty acids, sterols, flavonoids, and flavonolignans. Hydnocarpin, a flavonolignan, is reported to potentiate antimicrobial and anticancer activity. The extracts and compounds isolated from this plant show a wide spectrum of pharmacological properties, including antibacterial, antileprotic, antitubercular, antipsoriatic, antirheumatic, hypolipidemic, antidiabetic, anticancer, anti-inflammatory, and antioxidant activities. The antileprotic activity is postulated to be due to the cyclopentenyl fatty acids present in the seed oil. CONCLUSION: Flavonolignans have an interesting chemical motif, and hydnocarpin and its congeners should be investigated for their activities and the mechanism underlying these activities. Multi-drug-resistant microbes are on the increase, and the possible inhibitory effect of these compounds when used with current antimicrobials should also be evaluated. Furthermore, unique cyclopentenyl fatty acids should also be investigated to understand the exact mechanism of action underlying antileprotic activity. Additional in depth phytochemical investigations of seed oil and extracts are required to tap the true potential of species from the Hydnocarpus genus.

In vitro cytotoxic activity of menispermaceae plants against HeLa cell line.

BACKGROUND: Menispermaceae, a family of flowering plants, is a medium-sized family of 70 genera totaling 420 extant species, mostly of climbing plants. It has various medicinal properties, which are used in the Ayurvedic system of medicine. Plants belonging to this family are rich in alkaloids, especially bisbenzylisoquinoline type. The hypothesis of this study is that the bisbenzylisoquinoline alkaloids present in the selected plants may exhibit in vitro cytotoxic property. AIM: The present study is aimed at estimating the total alkaloidal content of methanolic extract of Cocculus hirsutus and Cissampelos pareira and evaluating the in vitro cytotoxic activity of both the extracts on the HeLa cell line. SETTINGS AND DESIGN: Methanolic extracts of both the plants in the concentrations of 500, 250, 125, 62.5, and 31.25 µg/ml were assessed for its cytotoxic activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. MATERIALS AND METHODS: Total alkaloidal content was studied for both the plants using ultraviolet-visible spectroscopy method. Methanol extracts of both the plants were tested for its inhibitory effect on HeLa cell line. Cytotoxicity of the plant extracts was evaluated by MTT assay. Nonlinear regression graph was plotted between % cell inhibition and Log10 concentration, and IC50 was determined using GraphPad Prism software. RESULTS: Preliminary phytochemical studies confirm the presence of alkaloids in both the plants. The total alkaloids present in C. hirsutus and C. pareira were found to be 0.252%w/w and 0.1656%w/w respectively. The IC50 values of C. hirsutus and C. pareria were found to be 111 µg/ml and 129.3 µg/ml respectively. CONCLUSION: From this study, it is observed that C. hirsutus and C. pareira have in vitro cytotoxic activity against HeLa cell line.

Evaluation of the antipsoriatic activity of Aloe vera leaf extract using a mouse tail model of psoriasis.

Aloe vera gel is used traditionally for the treatment of skin diseases, including psoriasis. An ethanolic extract of the gel was assessed for antipsoriatic activity using a mouse tail model of psoriasis. The extract produced a significant differentiation in the epidermis, as seen from its degree of orthokeratosis (85.07 ± 3.36%) when compared with the negative control (17.30 ± 4.09%). This was equivalent to the effect of the standard positive control, tazarotene (0.1%) gel, which showed a 90.03 ± 2.00% degree of orthokeratosis. The ethanolic extract of Aloe vera leaf gel also produced a significant increase in relative epidermal thickness when compared with the control group, whereas the standard tazarotene showed no change. Taken together, the extract showed an overall antipsoriatic activity of 81.95%, compared with 87.94 for tazarotene, in the mouse tail model for psoriasis.

Screening of Caesalpinia bonduc leaves for antipsoriatic activity.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Caesalpinia bonduc (L.) Roxb. (Caesalpiniaceae) have been used by traditional Siddha healer of Malabar region for psoriasis treatment. AIM OF THE STUDY: To evaluate the Caesalpinia bonduc decoction (CBD), Caesalpinia bonduc hydroalcoholic extract (CBHA) for antipsoriatic activity. MATERIALS AND METHODS: Mouse tail test for psoriasis was used for the evaluation of antipsoriatic activity. Extracts were tested at a dose of 500 mg/kg b.w. and fractions at 250 mg/kg b.w. in Swiss albino mice. Parameters studied in the mouse tail test were changes in epidermal thickness and percentage orthokeratotic values. In vitro antiproliferant assay on HaCaT cell lines and in vitro lipoxygenase inhibition were also carried out. RESULTS: Butanol fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAB) and water fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAW) produced significant orthokeratosis (p<0.001). In relative epidermal thickness, a significant (p<0.05) reduction with respect to control was observed in groups treated with retinoic acid, CBD, butanol fraction of Caesalpinia bonduc decoction (CBDB), water fraction of Caesalpinia bonduc hydroalcoholic extract (CBHAW). Maximum antiproliferant activity was shown by CBHA (IC(50), 77.5±12.7 µg/ml). In lipoxygenase inhibition assay, water fraction of Caesalpinia bonduc decoction (CBDW) showed maximum activity with an IC(50) value of 164.71±4.57 µg/ml. CONCLUSIONS: Among all the tested samples only CBHAW showed good activity in the mouse tail test, antiproliferant activity in HaCaT cells and lipoxygenase inhibition assay. Other extracts and fractions showed varying degrees of activity. The present study supports the traditional use of Caesalpinia bonduc leaves for psoriasis treatment.

Hypoglycemic activity of Nymphaea stellata leaves ethanolic extract in alloxan induced diabetic rats.

The ethanolic extract of leaves of Nymphaea stellata given by oral route to diabetic rats at dose of 100 and 200 mg/kg/day for seven days reduced significantly by 31.6 and 42.6 % the plasma glucose level increased by intraperitoneal injection of 120 mg/day of alloxan. Moreover, the treatment significantly affected the plasma level of cholesterol and triglyceride.

A comparative pharmacognostical evaluation of two Artemisia species found in Nilgiris biosphere.

Artemisia pallens Wall. ex DC commonly known as "Davana" in Kannada and Artemisia abrotanum Linn. known as "Southernwood" (Asteraceae) are aromatic herbs, erect in habit, upto 60 cm tall, leaves are very small, much divided, bluish green. These plants find use in traditional systems of medicine viz., anthelmintic, tonic and antipyretic properties. Since, these species have not been scientifically evaluated; the present study was aimed to bring these plants under a suitable pharmacognostical scheme.

Hepatoprotective activity of the Indian medicinal plant Polygala arvensis on D-galactosamine-induced hepatic injury in rats.

The suspensions of chloroform extract of leaves in 0.3% carboxy methyl cellulose (CMC) was evaluated for hepatoprotective activity in Wistar albino rats by inducing hepatic injury with d-galactosamine (400 mg/kg). The chloroform extract of Polygala arvensis at an oral dose of 200 mg/kg and 400 mg/kg exhibited a significant (P<0.001, P<0.01 and P<0.05) protection effect by normalizing the levels of aspartate amino transferase (ASAT, GOT), alanine amino transferase (ALAT, GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), total cholesterol (TC), triglycerides (TGL), albumin, total protein (TP) which were significantly (P<0.001) increased in rats by treatment with 400 mg/kg i.p. of d-galactosamine. Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001).

Hypoglycaemic activity of Pterocarpus marsupium Roxb.

The antidiabetic activity of various subfractions of the alcohol extract of the bark of Pterocarpus marsupium Roxb. was evaluated in alloxan-induced diabetic rats. The effect of these extracts on lipid profile and liver function tests were also assessed to evaluate their activity in controlling diabetes related metabolic alterations. The parameters measured were plasma glucose, total protein, cholesterol, triglycerides, alkaline phosphatase, SGOT and SGPT. The results indicate the effective role of Pterocarpus marsupium on the above mentioned parameters indicating that Pterocarpus marsupium can also control the diabetes related metabolic alterations apart from controlling the glucose levels. Among the fractions tested the butanol subfraction was found to be more active in comparison with other subfractions. It can be concluded that the butanol subfraction of the alcohol extract of Pterocarpus marsupium exhibits significant antidiabetic activity and corrects the metabolic alterations in diabetic rats and this activity may resemble insulin-like properties.

Hypoglycemic effect of ethanolic extract of Musa sapientum on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential.

The antihyperglycemic effect of ethanolic extract of flowers of Musa sapientum (Musaceae), a herb (used in Indian folklore medicine for the treatment of diabetes mellitus) in alloxan induced diabetic rats. Oral administration of the ethanolic extract showed significant (p < 0.001) blood glucose lowering effect at 200 mg/kg in alloxan induced diabetic rats (120 mg/kg, i.p.) and the extract was also found to significantly (p < 0.001) scavenge oxygen free radicals, viz., superoxide dismutase (SOD), catalase (CAT) and also protein, malondialdehyde and ascorbic acid in vivo. Musa sapientum induced blood sugar reduction may be due to possible inhibition of free radicals and subsequent inhibition of tissue damage induced by alloxan. The antidiabetic activity observed in this plant may be attributed to the presence of flavonoids, alkaloids, steroid and glycoside principles.

Pharmacognostical studies on leaves of ataiantia monophyia correa.

Leaves of Atalantia monophylla are used in chronic rheumatism and paralysis. The Pharmacognostical studies like histological characters, leaf constants, ash values and extractive values of leaves of Atalantia monophylla Corr were carried out. The preliminary phytochemical analysis were also carried out.