Review of Shikonin and Derivatives: Isolation, Chemistry, Biosynthesis, Pharmacology and Toxicology.

Shikonin and its derivatives, isolated from traditional medicinal plant species of the genus Lithospermum, Alkanna, Arnebia, Anchusa, Onosma, and Echium belonging to the Boraginaceae family, have numerous applications in foods, cosmetics, and textiles. Shikonin, a potent bioactive red pigment, has been used in traditional medicinal systems to cure various ailments and is well known for its diverse pharmacological potential such as anticancer, antithrombotic, neuroprotective, antidiabetic, antiviral, anti-inflammatory, anti-gonadotropic, antioxidants, antimicrobial and insecticidal. Herein, updated research on the natural sources, pharmacology, toxicity studies, and various patents filed worldwide related to shikonin and approaches to shikonin's biogenic and chemical synthesis are reviewed. Furthermore, recent studies to establish reliable production systems to meet market demand, functional identification, and future clinical development of shikonin and its derivatives against various diseases are presented.

Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan: A Comprehensive Review on Traditional Uses, Phytochemistry and Pharmacology.

The influence of medicinal plants on humanity spans time immemorial. These plants are also used at present with local and tribal peoples for the cures of various illnesses. Nature has produced an immense number of medicinal plants, which directly or indirectly help to treat various ailments and have numerous applications in the fields of pharmaceuticals, agriculture, food flavors and preservatives, aromas, and cosmetics. Bergenia pacumbis (Buch.-Ham. ex D.Don) C.Y.Wu & J.T.Pan (synonym: Bergenia ligulate Engl.), is an important medicinal plant belonging to the Saxifragaceae family, and not to be confused with Bergenia ciliata (Haw.) Sternb., and is popularly known as Pashanbheda (meaning to dissolve the kidney stone). This plant is a rich source of secondary metabolites (SMs) such as coumarins, flavonoids, benzenoids, lactones, tannins, phenols, and sterols, which make this plant a highly valued medicinal herb with a broad spectrum of pharmacological activities such as anti-urolithic, antioxidant, anti-viral, free radical scavenging, antidiabetic, anti-hepatotoxic, diuretic, antipyretic, anti-oxaluria, anti-tumour, antibacterial, antifungal, anti-inflammatory, antimicrobial, and cardioprotective. This review summarizes traditional uses and offers up to date data for future research on B. pacumbis.

Comprehensive review on ethnobotanical uses, phytochemistry, biological potential and toxicology of Parthenium hysterophorus L.: A journey from noxious weed to a therapeutic medicinal plant.

ETHNO-PHARMACOLOGICAL RELEVANCE: Parthenium hysterophorus L. is a noxious weed and a species of flowering plant in the Asteraceae family. It is regarded as the seventh most deadly weed in the world: harmful to both humans and livestock. It is widely known as Congress Grass or Feverfew. Despite its pitfalls, P. hysterophorus bestows medicinal effects. Although prolific in nature and difficult to control, many novel applications of this controversial herb have been discovered as an approach to manage the weed. AIM: The current review aims to compile all the ethnobotanical, phytochemistry, biological activities and utilities, clinical studies and toxicity data available on P. hysterophorus and its major chemical constituent parthenin. MATERIALS AND METHODS: Extensive literature surveyed Google search, Google scholar, Wiley online library, Elsevier, Springer, Science direct, American Chemical Society, Royal Society of Chemistry and Research Gate. RESULT: According to the study, P. hysterophorus is utilized as a traditional medicine throughout Central America and the Caribbean. It can be used to treat skin infections, dermatitis, amoebic dysentery, and as an analgesic in the treatment of muscular rheumatism. The extracts obtained from P. hysterophorus have anti-inflammatory, antioxidant, larvicidal, anti-microbial, insecticidal, hypoglycaemic and anti-cancer activity. CONCLUSION: The earlier investigations confirmed that P. hysterophorus has numerous traditional and biological applications. However, the scientific data are limited in clinical and toxicological studies. Therefore, further research is required on clinical and toxicological aspects to understand the complete potential and effects of P. hysterophorus.

The genus Nepeta: Traditional uses, phytochemicals and pharmacological properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Nepeta is a multiregional genus of the "Lamiaceae" (Labiatae or Mint) family. Species of Nepeta are a valuable part of traditional medicine and used extensively, particularly in the Himalayan region of India (Uttarakhand, Himachal Pradesh, Jammu and Kashmir, Leh-Ladakh), Pakistan (Khyber Pakhtunkhwaand Pakistani Kashmir), Nepal (Baglund district), also in China and hilly regions of Turkey and Iran. Nepeta species are extensively used as a remedy against a variety of ailments and conditions like chicken pox, tuberculosis, malaria, pneumonia, influenza, measles, stomach disorders, eye complaints, respiratory disorders, asthma, colds, coughs etc. AIM OF THE REVIEW: The main aim of this review is to present a comprehensive and detailed study on traditional uses, pharmacology, phytochemistry, toxicology of Nepeta species and suggest future direction on the design and conduct of various preparations, either alone or in blends with prevailing conventional remedies. The review also emphasizes encouraging researchers towards the wide range of pharmaceutical applications of the various species of Nepeta for their better use and exploration in the future. MATERIAL AND METHODS: All the relevant data and information on different species of Nepeta were assembled using different databases, such as Science Direct, Springer, PubMed, Taylor and Francis imprints, Chemspider, Google scholar, review and research articles from peer-reviewed journals and unpublished data. Some select 'grey literature' sources viz. ethnobotanical books, chapters, Wikipedia and webpages were also studied. RESULTS: A variety of bioactive secondary metabolites and nutraceuticals has been isolated from various species of Nepeta. These bioactive compounds belong to different classes of secondary metabolites, such as phenolic acids and their glycosides (rosmarinic acid, gallic acid, caffeic acid), flavonoids and their glycosides (cirsimaritin, salvigenin, luteolin, apigenin), iridoids (nepetalactones and their derivatives), terpenoids (1,8-cineole, linalool, ß-caryophyllene, germacrene D, parnapimaro, ß-amyrin, oleanolic acid, ursolic acid), steroids (ß-sitosterol, stigmasterol), lignans, amino acids, carbohydrates, volatile oils, etc. The species of the genus Nepeta possess a variety of pharmacological activities namely anti-inflammatory, anti-nociceptive, anti-alzheimer, anticancer and cytotoxic, antioxidant, immunomodulatory, antimicrobial, antifungal, insecticidal and along with other biological activities. CONCLUSION: The species of the genus Nepeta contains a rich source of various bioactive compounds, which are well tolerated as traditional medicines. In fact, different species of Nepeta are widely used in a variety of traditional medicinal systems all around the world. Owing to the variety of pharmacological properties of Nepeta species, more comprehensive and inclusive clinical trials are necessary for the utilization of different Nepeta species against the treatment of a wide range of ailments. There are also various other uses such as food, cosmetic and agriculture that can be investigated or explored in future. Some of the major domains that can be explored within this genus are the investigation of different species for their unexplored biological potential, isolation and characterization of new bioactive constituents and finally, investigation of new applications and possible commercialization of these bioactive leads. No doubt, there are various viable research domains outside those discussed above, but presently for the purposes of this review we will only emphasize the activities herein.

NMR Applications for Botanical Mixtures: The Use of HSQC Data to Determine Lignan Content in Sambucus williamsii.

Lignans found in the botanical extract of the Traditional Chinese Medicine Sambucus williamsii Hance exhibit protective effects on trabecular bone mass and mechanical strength of cortical bone of ovariectomized rats. A novel approach was adapted using HSQC NMR methods to estimate the total amount of these bioactives in a complex mixture. It was determined that lignans possessing the hydroxy- or oxybenzyl carbon signal were bioactive. These compounds were readily identified and assigned in a defined region of the 13C NMR spectrum at 80-90 ppm and calculated as 10-15% of the lignan-rich fraction of S. williamsii. Comparison of the peak heights of the oxybenzyl-substituted carbon resonance signals of the lignans in the botanical extract was made against those of a standard lignan pinoresinol. The application of this simple and reliable NMR method can be used to estimate amounts of related compounds and chemical families in complex mixtures or botanical extracts and offers measurable scientific evidence in quality processes. This is of particular importance for registration requirements of botanical drugs and in complex mixtures of botanical extracts.

Phytochemicals and potential health effects of Sambucus williamsii Hance (Jiegumu).

Sambucus williamsii Hance (Jiegumu) is traditionally used in Chinese medicine to treat bone and joint diseases. The major phytochemicals in S. williamsii are lignans, terpenoids, and phenolic acids, together with trace amounts of essential oils, minerals, amino acids, and natural pigments. In this review, a database search for studies published from 1990 to November 2015 was conducted using PubMed, the China Academic Journals Full-Text Database, and Google Scholar with the keywords "Sambucus williamsii Hance", "Sambucus williamsii", "Sambucus williamsii + clinic", "Sambucus williamsii + biology", "Sambucus williamsii + chemicals", and "Jiegumu", which covered chemical studies, cell culture studies, animal experiments, and clinical studies. This article reviewed the compounds isolated from S. williamsii that may reduce the risk of cancer, and exert antifungal, antioxidant, anti-inflammatory, bone fracture healing, and antiosteoporotic effects.

Re-discovering ancient wheat varieties as functional foods.

With the gluten-free food market worth almost $1.6 bn in 2011, there is every reason for renewed interest in ancient grains. This resurgent interest is expressed in re-discovering ancient varieties as functional foods. In particular, people affected by celiac disease have to avoid all gluten in their diet and several ancient grains may offer an important alternative.

Green tea and theanine: health benefits.

Historically, the medicinal use of green tea dates back to China 4700 years ago and drinking tea continues to be regarded traditionally in Asia as a general healthful practice. Numerous scientific publications now attest to the health benefits of both black and green teas, including clinical and epidemiological studies. Although all tea contains beneficial antioxidants, high-quality green and white teas have them in greater concentrations than black tea. Today, scientists believe that the main active ingredients of green tea include the polyphenols, in particular the catechins and the amino acid, theanine. Studies on the health benefits of drinking tea, particularly green tea, are finding exciting results, particularly in cancer research. Modern studies in both Asia and the West have provided encouraging results indicating that drinking green tea contributes to fighting many different kinds of cancers including stomach, oesophageal, ovarian and colon. Recent studies describing the health benefits of these compounds will be reviewed.

Use of quantitative flow cytometry to measure ex vivo immunostimulant activity of echinacea: the case for polysaccharides.

INTRODUCTION: When directly exposed to various echinacea fractions, human leukocytes ex vivo are strongly stimulated to proliferate and to produce immunostimulation and inflammatory cytokines. A comparison of fractions containing lipoidal small molecules and high-molecular-weight water-soluble polysaccharides indicates that the latter are substantially more potent as immunostimulants. Echinacea purpurea (L.) Moench, E. angustifolia DC, and E. pallida (Nutt.), Nutt. extracts, and each plant part contain significantly potent constituents. Flow cytometric techniques were utilized. OBJECTIVES: This study was undertaken to determine whether flow cytometry could measure immunostimulant activity present in echinacea and, if so, which species produced more activity, which plant part was the most active, and whether the organic soluble or the aqueous extractables were more active. Ex vivo human clinical material was employed. DESIGN: Echinacea extracts were analyzed using flow cytometric techniques. The immunostimulation assays were measured in triplicate. METHODS: Samples dissolved in dimethyl sulfoxide (DMSO) were added to 200 microL of heparinized blood mixed with 50 muL of phosphate buffer, vortexed, and incubated to allow adequate time for immune-cell stimulation. Fifty (50) microL of the stimulated blood samples were added to each of a reagent cocktail consisting of 20 microL of CD4FITC/CD69PE/CD3PerCP expressed on the helper/inducer T-lymphocyte subset; CD8FITC/CD69/PE/ CD3PerCP expressed on the human suppresser/cytotoxic T-lymphocytes and on a subset of natural killer lymphocytes; CD19FITC/CD69PE/CD45PerCP expressed on B-lymphocytes; or CD56FITC/CD69PE/CD45PerCP expressed on NK lymphocytes. Four hundred and fifty (450) microL of 1 X FACS lysing solution was added and incubated in the dark (rt, 30 minutes) and then subjected to flow cytometric analysis. All reported readings are the average of several determinations. Positive controls consisted of phorbol myristyl acetate (PMA) (50 ng/mL), phytohemagglutinin (10 microg/mL), CD2/CD2R (positive activation control)(5 microL/250 muL of reaction), and negative controls consisted of dimethyl sulfoxide (2% in RPMI-1640), RPMI-1640 medium, and cyclosporin A (10 microg/mL). RESULTS: The main immunostimulatory activity of echinacea resides in the water-soluble materials rather than the lipoidal small molecules. E. purpurea, E. Pallida, and E. angustifolia leaves, stems, flowering tops, and roots all produce substantial immunostimulatory activity. CONCLUSIONS: The use of flow cytometry demonstrates a link between the polysaccharides in echinacea and the biologic immunostimulatory effect that has therapeutic relevance, and strong evidence for this immunostimulant property is presented.

Dysoxylins A-D, tetranortriterpenoids with potent anti-RSV activity from Dysoxylum gaudichaudianum.

Four new compounds, belonging to the tetranortriterpenoid family, named dysoxylins A-D (1-4), isolated from Dysoxylum gaudichaudianum, were found to exhibit potent antiviral activity against respiratory syncytial virus (RSV). These structures were determined by NMR spectroscopy and mass spectrometry and were shown to have anti-RSV EC50 activities in the range 1.0-4.0 microg/mL in cytopathic effect inhibition and plaque reduction assays.

Medicinal benefits of green tea: part II. review of anticancer properties.

Currently there is wide interest in the medicinal benefits of green tea (Camellia sinensis). Tea is one of the most widely consumed beverages in the world, and extracts of tea leaves are also sold as dietary supplements. Green tea extracts contain a unique set of catechins that possess biologic activity in antioxidant, antiangiogenesis, and antiproliferative assays that are potentially relevant to the prevention and treatment of various forms of cancer. With the increasing interest in the health properties of tea and a significant rise in their scientific investigation, it is the aim of this review to summarize recent findings on the anticancer and medicinal properties of green tea, focusing on the biologic properties of the major tea catechin, (-)-epigallocatechin and its antitumor properties.

Medicinal benefits of green tea: Part I. Review of noncancer health benefits.

Tea, in the form of green or black tea, is one of the most widely consumed beverages in the world. Extracts of tea leaves also are sold as dietary supplements. However, with the increasing interest in the health properties of tea and a significant rise in scientific investigation, this review covers recent findings on the medicinal properties and noncancer health benefits of both green and black tea. In Part II, a review of anticancer properties of green tea extracts is presented. Green tea contains a unique set of catechins that possess biological activity in antioxidant, anti-angiogenesis, and antiproliferative assays potentially relevant to the prevention and treatment of various forms of cancer. Although there has been much focus on the biological properties of the major tea catechin epigallocatechin gallate (EGCg) and its antitumor properties, tea offers other health benefits; some due to the presence of other important constituents. Characteristics unrelated to the antioxidant properties of green and black teas may be responsible for tea's anticancer activity and improvement in cardiac health and atherosclerosis. Theanine in green tea may play a role in reducing stress. Oxidized catechins (theaflavins in black tea) may reduce cholesterol levels in blood. Synergistic properties of green tea extracts with other sources of polyphenolic constituents are increasingly recognized as being potentially important to the medicinal benefits of black and green teas. Furthermore, due to presumed antioxidant and antiaging properties, tea is now finding its way into topical preparations. Each of these aspects is surveyed.

Tea catechin synergies in inhibition of cancer cell proliferation and of a cancer specific cell surface oxidase (ECTO-NOX).

The anticancer properties of tea catechins are most frequently attributed to the principal catechin (-)-epigallocatechin-3-gallate (EGCg). Efficacy was evaluated using growth of cultured HeLa cells and inhibition of the enzymatic activity of a putative cell surface tea target enzyme, a cancer-associated cell surface-located NADH oxidase (ECTO-NOX) designated tNOX. The amounts of EGCg required to inhibit by both criteria was reduced 10 times by combination with inactive catechins such as (-)-epicatechin (EC), (-)-epigallocatechin (EGC) or (-)-epicatechin-3-gallate (ECG). Various synthetic mixtures based on purified catechins and decaffeinated tea extracts treated enzymatically to reduce the ester bond-containing catechins varying in EGCg content from 0.065 to 40% were of comparable efficacy to decaffeinated green tea extracts as long as EGCg was present and the ratio of total catechins to EGCg + EGC was about 1.5. Such mixtures appear to offer potential cancer protection and therapeutic advantages over those of EGCg alone through lowered toxicity of the mixture to normal cells and for more efficient blood delivery of orally-administered catechins to a tumour site.

CordyMax Cs-4 improves glucose metabolism and increases insulin sensitivity in normal rats.

OBJECTIVE: To evaluate effects of CordyMax trade mark Cs-4, a mycelial fermentation product of Cordyceps sinensis, on improving glucose metabolism and insulin sensitivity. DESIGN: An in vivo pharmacology study. Subjects and Study Interventions: Adult Wistar rats, male and female, were given CordyMax 250 or 500 mg/kg per day or placebo for 17 days by gavage. OUTCOME MEASUREMENTS: Fasting blood glucose, fasting plasma insulin, glucose-insulin index, and oral glucose tolerance. RESULTS: Rats fed Cs-4 at either 250 or 500 mg/kg showed significantly reduced fasting blood glucose after the 17-day treatment, by 27% and 24% from baselines respectively (both p < 0.001). Examination of fasting plasma insulin demonstrated a 37% decrease in the high dose treatment groups (p = 0.012). Glucose-insulin index, an index of insulin sensitivity, increased by 10% and 17% in both 250 and 500 mg/kg groups (p = 0.008 and p = 0.0001, respectively). Oral glucose tolerance tests showed significantly improved glucose tolerance at 0.5, 1.0, and 2.0 hours after oral administration of a bolus of glucose (the area under the glucose curve: p = 0.05-0.006), but no change at 5 hours. CONCLUSION: CordyMax Cs-4 is effective in lowering basal blood glucose and plasma insulin, improving glucose metabolism by enhancing insulin sensitivity, and improving oral glucose tolerance.

New lanostanoids from the mushroom Ganoderma lucidum.

From a lipophilic extract of the fruiting body of Ganoderma lucidum, three new lanostanoids, 8beta,9alpha-dihydroganoderic acid J (1), methyl 8beta,9alpha-dihydroganoderate J (2), and 20-hydroxylganoderic acid G (3), along with 12 known lanostanoids and two ergostane sterols were isolated. The structures of 1-3 were determined by interpretation of their spectroscopic data.