Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases.

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases.

New perspectives for natural triterpene glycosides as potential adjuvants.

BACKGROUND: Triterpene glycosides are a vast group of secondary metabolites widely distributed in plants including a high number of biologically active compounds. The pharmacological potential is evaluated by using many bioassays particularly in the field of cancerology, immunology, and microbiology. The adjuvant concept is well known for these molecules in vaccines, but there is little preclinical evidence to support this concept in the management of cancer, infections and inflammation. PURPOSE: We aim to review some examples of triterpene glycosides from natural sources which exhibit adjuvant activity when they are co-adminitered with anticancer drugs, targeted toxins, antimicrobial, anti-inflammatory drugs and with antigens in vaccines. METHODS: The scientific literature on the adjuvant potential of triterpene glycosides covering mainly the last two decades has been identified by using relevant key words in the databases, using the online service such as Medline/PubMed, Scopus, Web of Science, Google Scholar. RESULTS: We divided these findings in four kind of examples, the combination of triterpene glycosides (1) with chemotherapeutic agents in conventional tumor therapies and with targeted toxins, (2) with antimicrobial drugs, (3) with antiinflammatory drugs, and (4) with an antigen in prophylactic and therapeutic vaccines. Pharmacological studies have revealed that some triterpene glycosides co-administered with anticancer drugs such as cisplatin, paclitaxel, cyclophosphamide, etoposide, 5-fluorouracyl, mitoxantrone exhibited increased cytotoxicity in tumor cells better than when the drugs were administered alone. However in vivo toxicological and pharmacokinetic studies are required before the combination strategy can be applied into clinical practice. Other studies showed that combined application of triterpene glycosides with targeted toxins resulted in the increased efficacy of the toxin, simultaneously reducing the dosage, and side effects. It was also shown that the co-administration of the triterpenoids with corticosteroids synergistically inhibited the inflammatory response induced by carrageenan in rats. The search for new alternative adjuvants in vaccines in comparison with the aluminium salts inducing only a Th2-type immune response resulted in the discovery of the promising purified fraction QS-21 from Quillaja saponaria, which has been used in the development of a variety of prophylactic and therapeutic vaccines. Over 120 clinical trials for around 20 vaccine indications in infectious diseases, cancer, degenerative disorders have been reported involving more than 50,000 patients. CONCLUSION: This review summarized the successfull in vitro and in vivo studies showing that this combination approach of triterpene glycosides co-adminitered with anticancer, antimicrobial and anti-inflammatory drug may provide an exciting road for further developments in the treatment of some cancers, parasitic and inflammatory diseases and in the rational design of vaccines against infectious diseases and cancer. From a clinical point of view, the potential benefit of QS-21, a promising triterpene glycoside from Quillaja saponaria has been highlighted in several vaccine clinical trials with a favorable ratio efficacy/toxicity.

Introduction: Novel hybrid combinations containing synthetic or antibiotic drugs with plant-derived phenolic or terpenoid compounds.

BACKGROUND: There is a paradigm shift in chemotherapy from mono-drug therapy towards multidrug combination regimens. Natural products from medicinal plants may play an important role for the design of novel combination therapy protocols. HYPOTHESIS: We introduce the novel term "hybrid combination" for the therapeutic combination of chemically defined plant-derived constituents (e.g. phenolic or terpenoid compounds with synthetic or antibiotic drugs to increase pharmacological activity and simultaneously toxic side effects. STUDY DESIGN: Several literature databases were screened on the combination of phenolic/terpenoid compounds with synthetic/antibiotic drugs. RESULTS: Phenolic compounds are water soluble and interact with target proteins due to their OH-groups. They reveal antioxident, antiinflammatory and sometimes apoptotic activities whereas the terpenoids possess due to their lipophilic nature together with the phenolics amphiphilic properties and thereby good cell-penetrating features. They reveal antioxidant properties, anti-inflammatory and sometimes apoptotic activities as well as cell-penetrating features due to their amphiphilicity. Synergistic or antagonistic interactions with synthetic or antibiotic drugs have to be demonstrated by using suitable methods (e.g. isobologram analysis). The molecular modes of action may be elucidated by approaches of network pharmacology (e.g. protein-protein interaction networks). CONCLUSION: There is convincing evidence for the improvement of pharmacological activity at reduced side effects by hybrid combinations. Future efforts should focus on clinical trials with hybrid combinations to treat a broad range of diverse diseases such as cardiometabolic and neurotropic syndromes, drug resistance phenotypes, and so-called neglected infectious diseases.

New Analytical Monographs on TCM Herbal Drugs for Quality Proof.

Regardless of specific national drug regulations there is an international consensus that all TCM drugs must meet stipulated high quality standards focusing on authentication, identification and chemical composition. In addition, safety of all TCM drugs prescribed by physicians has to be guaranteed. During the 25 years history of the TCM hospital Bad Kötzting, 171 TCM drugs underwent an analytical quality proof including thin layer as well as high pressure liquid chromatography. As from now mass spectroscopy will also be available as analytical tool. The findings are compiled and already published in three volumes of analytical monographs. One more volume will be published shortly, and a fifth volume is in preparation. The main issues of the analytical procedure in TCM drugs like authenticity, botanical nomenclature, variability of plant species and parts as well as processing are pointed out and possible ways to overcome them are sketched.

Bergenia crassifolia (L.) Fritsch--pharmacology and phytochemistry.

PURPOSE: Bergenia crassifolia (L.) Fritsch, a species in the Bergenia genus belongs to the family Saxifragaceae, is valuated for its medicinal application. The review focuses on the medicinal uses, phytochemistry, and the biological activities of B. crassifolia to explore its benefits and potential uses. METHODS: In this review, we summarized data, published in Russia and in other countries related to B. crassifolia. RESULTS: Rhizomes and leaves of this plant are in use as traditional remedies for the treatment of different disorders in the folk medicine systems of Russia and Asia. The plant is a potential source of tannins, benzanoids, flavonoids, polysaccharides and other active compounds. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb and individual compounds, which include adaptogenic, antiinflammatory, antihypertensive, antimicrobial, antioxidant, antiobesity, antitussive, cerebro-protective, hepatoprotective, immunomodulating, and diuretic. CONCLUSION: The review highlights the potential of B. crassifolia for further development of herbal medicines on its base.

Medicinal plants of the Russian Pharmacopoeia; their history and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Due to the location of Russia between West and East, Russian phytotherapy has accumulated and adopted approaches that originated in European and Asian traditional medicine. Phytotherapy is an official and separate branch of medicine in Russia; thus, herbal medicinal preparations are considered official medicaments. The aim of the present review is to summarize and critically appraise data concerning plants used in Russian medicine. This review describes the history of herbal medicine in Russia, the current situation and the pharmacological effects of specific plants in the Russian Pharmacopoeia that are not included in the European Pharmacopoeia. MATERIALS AND METHODS: Based on the State Pharmacopoeia of the USSR (11(th) edition), we selected plant species that have not yet been adopted in Western and Central Europe (e.g., selected for inclusion in the European Pharmacopoeia) and systematically searched the scientific literature for data using library catalogs, the online service E-library.ru, and databases such as Medline/Pubmed, Scopus, and the Web of Science regarding species, effectiveness, pharmacological effects, and safety. RESULTS: The Russian Federation follows the State Pharmacopoeia of the USSR (11(th) edition), which contains 83 individual plant monographs. Fifty-one of these plants are also found in the European Pharmacopoeia and have been well studied, but 32 plants are found only in the Pharmacopoeia of the USSR. Many articles about these medicinal plants were never translated in English, and much of the information collected by Russian scientists has never been made available to the international community. Such knowledge can be applied in future studies aimed at a safe, evidence-based use of traditional Russian medicinal plants in European and global phytopharmacotherapy as well as for the discovery of novel leads for drug development. CONCLUSION: The review highlights the therapeutic potential of these Russian phytopharmaceuticals but also highlights cases where concern has been raised about product safety and tolerability, which would aid in supporting their safe use.

Tetra-acetylajugasterone a new constituent of Vitex cienkowskii with vasorelaxant activity.

Tetra-acetylajugasterone C (TAAC) was found to be one of the naturally occurring compounds of the Cameroonian medicinal plant Vitex cienkowskii which is responsible for a vasorelaxant activity of an extract of this plant. The evaluation of the underlying mechanisms for the relaxing effect of TAAC was determined using aortic rings of rats and mice. TAAC produced a concentration-dependent relaxation in rat artery rings pre-contracted with 1µM noradrenaline (IC50: 8.40µM) or 60mM KCl (IC50: 36.30µM). The nitric oxide synthase inhibitor l-NAME (100µM) and the soluble guanylate cyclase inhibitor ODQ (10µM) significantly attenuated the vasodilatory effect of TAAC. TAAC also exerted a relaxing effect in aorta of wild-type mice (cGKI(+/+); IC50=13.04µM) but a weaker effect in aorta of mice lacking cGMP-dependent protein kinase I (cGKI(-/-); IC50=36.12µM). The involvement of calcium channels was studied in rings pre-incubated in calcium-free buffer and primed with 1µM noradrenaline prior to addition of calcium to elicit contraction. TAAC (100µM) completely inhibited the resulting calcium-induced vasoconstriction. The same concentration of TAAC showed a stronger effect on the tonic than on the phasic component of noradrenaline-induced contraction. This study shows that TAAC, a newly detected constituent of Vitex cienkowskii contributes to the relaxing effect of an extract of the plant. The effect is partially mediated by the involvement of the NO/cGMP pathway of the smooth muscle but additionally inhibition of calcium influx into the cell may play a role.

Identification of isosilybin a from milk thistle seeds as an agonist of peroxisome proliferator-activated receptor gamma.

Peroxisome proliferator-activated receptor gamma (PPARγ) is a key regulator of glucose and lipid metabolism. Agonists of this nuclear receptor are used in the treatment of type 2 diabetes and are also studied as a potential treatment of other metabolic diseases, including nonalcoholic fatty liver disease. Silymarin, a concentrated phenolic mixture from milk thistle (Silybum marianum) seeds, is used widely as a supportive agent in the treatment of a variety of liver diseases. In this study, the PPARγ activation potential of silymarin and its main constituents was investigated. Isosilybin A (3) caused transactivation of a PPARγ-dependent luciferase reporter in a concentration-dependent manner. This effect could be reversed upon co-treatment with the PPARγ antagonist T0070907. In silico docking studies suggested a binding mode for 3 distinct from that of the inactive silymarin constituents, with one additional hydrogen bond to Ser342 in the entrance region of the ligand-binding domain of the receptor. Hence, isosilybin A (3) has been identified as the first flavonolignan PPARγ agonist, suggesting its further investigation as a modulator of this nuclear receptor.

Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex cienkowskii Kotschy & Peyritsch is a deciduous tree, prescribed by Cameroonian traditional healers as one of the most popular plant widely used in many disorders including cardiovascular diseases. The preliminary pharmacological studies carried out on Vitex cienkowskii showed its vasorelaxant activities on guinea-pig aortic rings. AIM OF THE STUDY: The present work evaluated the vasorelaxant activity of extract and isolated compounds from Vitex cienkowskii. MATERIALS AND METHODS: Rat aortic rings were used to evaluate the in vitro vascular effect of the extract. The antioxidant activity was determined by measuring the reduction of the free radical 1,1-diphenyl-1-picryl-hydrazyl (DPPH). RESULTS: Vitex cienkowskii induced significant relaxation in a concentration- and endothelium-dependent manner (EC(50)=12.12 µg/ml, CH(2)Cl(2)-MeOH, 1:1) and did not produce a vasorelaxant effect on contraction evoked by KCl (60 mM). In order to determine its mode of action, Vitex cienkowskii-induced relaxant effect was evaluated in the presence of indomethacin (10 µM), L-NAME (100 µM), ODQ (1 µM) and SQ22356 (100 µM). Relaxation was significantly blocked by L-NAME and ODQ. These results indicate that Vitex cienkowskii-mediated relaxation is endothelium dependent, probably due to NO release, and the consequent activation of vascular smooth muscle soluble guanylate cyclase (sGC), a signal transduction enzyme that forms the second messenger cGMP. Bio-guided study of Vitex cienkowskii allowed the isolation of the known pentacyclic triterpenoids and a ceramide. It is the first report of salvin A, maslinic acid and a ceramide from Vitex cienkowskii. The activity induced by these compounds indicated that they may be partly responsible for the vasorelaxant effect of the plant extract. A dose of 40 mg/kg of CH(2)Cl(2)-MeOH (1:1) extract administered intravenously induced a decrease of mean arterial pressure but did not affect the heart rate. Moreover the plant extracts were found to be highly active in the DPPH radical scavenging assay. CONCLUSION: Vitex cienkowskii extract possesses antioxidant property, vasorelaxing, and hypotensive effect linked to the endothelium related factors, where nitric oxide is involved.

Development of an LC-MS method for simultaneous quantitation of amentoflavone and biapigenin, the minor and major biflavones from Hypericum perforatum L., in human plasma and its application to real blood.

INTRODUCTION: Biflavones of Hypericum perforatum L. are bioactive compounds used in the treatment of inflammation and depression. Determination of amentoflavone and biapigenin from blood is challenging owing to their similar structures and low concentrations. OBJECTIVE: To develop a rapid, sensitive and accurate method based on liquid-phase extraction followed by high-performance liquid chromatography and electrospray ionisation mass spectrometry (HPLC-ESI-MS) for quantification of biflavones in human plasma. METHODOLOGY: After extraction from blood, the analytes were subjected to HPLC with an XTerra® MS C(18) column and a binary mobile phase consisting of 2% formic acid in water and acetonitrile under isocratic elution conditions, with ESI-MS detection in the negative ion mode and multiple reaction monitoring (MRM). RESULTS: Both calibration curves showed good linearity within the concentration range 1-500 ng/mL. Limits of detection (S/N = 3) were 0.1 ng for pure substances and the limits of quantitation (S/N = 5) were 1.0 ng/mL from analyte-spiked serum. The grand mean recovery was 90% from several subsamples of each biflavone. The imprecision (RSD) of peak areas was between 5% (intraday) and 10% (interday) for high concentrations (250 ng/mL) and between 10% (intraday) and 15% (interday) for low concentrations (1 ng/mL). Inaccuracy of the mean was less than 20% at the lower limit of quantitation. CONCLUSION: The developed and validated method for determination of biflavones from human plasma was effectively applied to pharmacokinetic studies of 13 probands and preliminary results indicate biphasic concentration-time curves.

Synergy research: approaching a new generation of phytopharmaceuticals.

The longstanding, successful use of herbal drug combinations in traditional medicine demands that we find a rationale for their comparative pharmacological and therapeutic superiority to isolated single constituents. The synergistic efficacy of these combinations can be evaluated and verified by Berenbaum's isobole method, followed by clinical studies performed in comparison with synthetic standard drugs. There are many examples of mono- and multi-extract combinations used presently, which exhibit synergistic efficiency based on multi-target mechanisms of action. Among the natural products, gallocatechins of green tea and curcuminoids of ginger are the presently favoured polyphenols for a possible future use in co-medication with antibiotics and standard anticancer drugs. The main targets were found to be COX 1+2, NF-κB, and membrane glycoproteins that belong to the ATP-binding cassette (ABC) transporter family.

Synergy research: a new approach to evaluating the efficacy of herbal mono-drug extracts and their combinations.

Synergy research is a new approach to phytomedicinal research. Three events have promoted this development: (1) The demand of the European drug law that the registration of drug preparations must include an assessment that each component of a herbal drug combination contributes to its overall pharmacological effect and therapeutic efficacy; (2) The availability of new high-tech analytical and molecular-biological methods and (3) A conspicuous change of paradigm in conventional medicine from a monodrug concept of treating diseases to a more multidrug therapy.

In vitro antiplasmodial activity of extract and constituents from Esenbeckia febrifuga, a plant traditionally used to treat malaria in the Brazilian Amazon.

Esenbeckia febrifuga (Rutaceae) is a plant traditionally used to treat malaria in the Brazilian Amazon region. Ethanol extract of stems displayed a good antiplasmodial activity against Plasmodium falciparum strains W-2 (IC(50) 15.5+/-0.71 microg/ml) and 3 D7 (IC(50) 21.0+/-1.4 microg/ml). Two coumarins (bergaptene 1 and isopimpinellin 2), five alkaloids (flindersiamine 3, kokusaginine 4, skimmiamine 5, gamma-fagarine 6 and 1-hydroxy-3-methoxy-N-methylacridone, 7), besides a limonoid (rutaevine 8), have been isolated for the first time from this species. Antiplasmodial activity of compounds 3, 5-8 has been evaluated in vitro against P. falciparum strains (W-2 and 3D7) and the furoquinolines 5 and 6 were the most potent displaying IC(50) values <50 microg/ml; flindersiamine (3) showed a weak activity while alkaloid 7 and rutaevine (8) were inactive (IC(50)>100 microg/ml).

Aplicación de las tecnologías ómicas a la Fitoterapia / No disponible

La demostración de la eficacia de los preparados fitoterápicos y la determinación de sus mecanismos de acción son retos permanentes para la fitoterapia basada en la evidencia. La genómica, proteómica y metabolómica son tecnologías de alto rendimiento, que permiten detectar simultáneamente un gran número de proteínas/genes, así como relacionar mezclas complejas con efectos complejos en forma de perfiles de expresión génica/proteica. La descripción de perfiles de expresión específicos para un determinado preparado fitoterápico puede ser útil para su estandarización química y farmacológica, así como para la evaluación de su toxicidad. A largo plazo, pueden economizar los estudios de eficacia y de mecanismos de acción, y facilitar la investigación de extractos vegetales carentes de principio(s) activo(s) predominantes. Se ha descubierto que los perfiles de expresión génica inducidos por fármacos individuales o sus combinaciones pueden ser completamente diferentes. La aplicación de las tecnologías “ómicas” puede suponer un cambio de paradigma en cuanto a la aplicación de mezclas complejas en medicina y abrir nuevos campos como la fitogenómica, fitoproteómica y fitometabolómica (AU)

The proof of efficacy of phytopreparations and the determination of their mode of action are permanent challenges for an evidence-based phytotherapy. Genomics, proteomics and metabolomics are high-throughput technologies that allow the simultaneous detection of a high number of proteins/genes and have the potential to relate complex mixtures to complex effects in the form of gene/ protein expression profiles. The development of phytopreparation-specific expression profiles will be useful for its chemical and pharmacological standardization and its toxicological assessment. Over a long-term perspective they may economize the studies on efficacy and mode of action of phytomedicines and allow to investigate herbal extracts without prominent active principle(s). The application of genomics revealed already that the gene expression profiles induced by single drugs and their combinations can be entirely different. The application of the “-omic-” technologies may lead to a change of paradigms towards the application of complex mixtures in medicine and open the new fields of phytogenomics, -proteomics and -metabolomics (AU)

[STW 5/Iberogast: multi-target-action for treatment of functional dyspepsia and irritable bowel syndrome]. / STW 5/Iberogast: Multi-Target-Wirkung bei funktioneller Dyspepsie und Reizdarmsyndrom.

Functional gastro-intestinal diseases such as functional dyspepsia and irritable bowel syndrome are a therapeutic challenge, as they are not only characterized by a multitude of symptoms, some of them with severe consequences for affected patients, but are also caused by a multitude of factors. The clinical efficacy of the therapeutics STW 5/Iberogast in these diseases has been proven in a number of randomized prospective clinical studies. Several preclinical studies suggest that its efficacy could be due to its complex composition of nine standardized herbal extracts, which act differently on multiple sites. This principle, which is quite popular in clinical medicine, was introduced as a multi-target therapy for functional bowel disorders. Components of STW 5/Iberogast reduce gastro-intestinal hypersensitivity and act spasmolytic on spastic, tonicising on atonic gastro-intestinal muscle. In addition a stimulating effect on reduced mucus-secretion, an inhibitory effect on enhanced gastric acid secretion and an anti-inflammatory effect have been shown. These effects could explain the clinical efficacy of STW5/Iberogast in a large range of symptoms.

A comprehensive review on nettle effect and efficacy profiles, Part I: herba urticae.

Nettle herb is recommended for complaints associated with rheumatoid arthritis, osteoarthritis and urinary tract infections. We therefore conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this plant material. Although clinical and experimental studies suggest that nettle herb has some anti-inflammatory properties, clinical evidence beyond doubt is lacking. Nettle preparations exert a number of promising in vitro and in vivo effects, however, further studies are needed to support these results and to find out if these effects are surrogates for clinical relevant effects in humans.

A comprehensive review on the stinging nettle effect and efficacy profiles. Part II: urticae radix.

Nettle root is recommended for complaints associated with benign prostatic hyperplasia (BPH). We therefore conducted a comprehensive review of the literature to summarise the pharmacological and clinical effects of this plant material. Only a few components of the active principle have been identified and the mechanism of action is still unclear. It seems likely that sex hormone binding globulin (SHBG), aromatase, epidermal growth factor and prostate steroid membrane receptors are involved in the anti-prostatic effect, but less likely that 5alpha-reductase or androgen receptors are involved. Extract and a polysaccharide fraction were shown to exert anti-inflammatory activity. A proprietary methanolic nettle root extract and particular fractions inhibited cell proliferation. Isolated lectins (UDA) were shown to be promising immunomodulatory agents, having also anti-viral and fungistatic effects. However, despite these in vitro studies it is unclear whether the in-vitro or animal data are a surrogate for clinical effects. The clinical evidence of effectiveness for nettle root in the treatment of BPH is based on many open studies. A small number of randomised controlled studies indicate that a proprietary methanolic extract is effective in improving BPH complaints. However, the significance and magnitude of the effect remains to be established in further confirmatory studies before nettle root treatment may be accepted in the guidelines for BPH treatment. The risk for adverse events during nettle root treatment is very low, as is its toxicity. Pre-clinical safety data remain to be completed.

Extraction of bioactive principles from Mucuna pruriens seeds.

Mucuna pruriens (L.) DC. Syn. M. prurita Hook. (Papilionaceae) is used in male impotency, as aphrodisiac, in sexual debility, and as nervine tonic. It also possesses anti-parkinson property, possibly due to the presence of L-DOPA. In the present study, attempts were made to develop the suitable method(s) for extraction of L-DOPA/other active components from the seeds using different solvents. The various extracts were also screened for their neuroprotective and antioxidant activities. In addition, TLC and HPLC fingerprinting of the extracts for amino acid components were also developed for preliminary and sophisticated analysis. The L-DOPA could be obtained in good yield on extraction with EtOH-H2O mixture (1:1) using ascorbic acid as protector. Interestingly, n-propanol extract, which contained negligible amount of L-DOPA, had shown significant neuroprotective activity, suggesting that some components, other than L-DOPA, might also be responsible for anti-Parkinson property of seeds. The extract (MW-0100) containing mainly amino acids and water-ethanol extract (1:1) (MWEL-1299) showed promising antioxidant activity (EC50 = 2.5 microg) against DPPH radicals. MWEL-1299 also exhibited encouraging results against 1-methyl-4-phenylpyridinium ion (MPP+) toxicity. The TLC fingerprinting may be used to authenticate the plant material in herbal industry.