sign in sign up
<<
Home , Equisetales, Equisetum, Equisetum arvense

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

Equisetum arvense: Ethanopharmacological and Phytochemical review with reference to osteoporosis

Smita Badole1# and Swati Kotwal2#

#1University Department of Biochemistry, RTM Nagpur University, Amravati Road, Nagpur 440033, , Mobile No.: 09730598174 #2University Department of Biochemistry, RTM Nagpur University, Amravati Road, Nagpur 440033, India, Mobile No.: 09665054511 ABSTRACT Osteoporosis is a skeletal disease characterized by bone loss and structural deterioration of the bone tissue, leading to increased bone fragility and susceptibility to fractures, most frequently in the hip, wrist and spine. There is imbalance between bone formation (osteoblastic activity) and bone resorption process (osteoclastic activity) due to various causes such as deficiency of estrogen hormone as in post menopausal osteoporosis, aging and oxidative stress. From ancient times many medicinal herbs have been reported in literature to treat osteoporosis. arvense (common horsetail) is one such herb which is suggested for the treatment of osteoporosis because of its very high silica content in the whole kingdom. Silica helps in the absorption and use of calcium and also in the formation of collagen. Also secondary metabolites such as flavonoids (quercetin, kaempferol, luteolin and apigenin) and triterpenoids (oleanolic acid, betulinic acid and ursolic acid) have shown protective effect in osteoporotic bone loss. The present review is an attempt to bring out the therapeutic properties of E. arvense in preventing and treating osteoporosis.

Key words: Osteoporosis; ; Silica; Flavonoids; Triterpenoids; Collagen

Abbreviations: SERMs, selective estrogen receptor modulators; BMP-2, Bone Morphogenetic protein-2; BMP-4, Bone Morphogenetic protein-4; Runx 2, runt related transcription factor 2; IL-6, Interleukin-6; TNFα, Tumour Necrosis Factor alpha; COX-2, Cyclooxigenase-2; PGE2, prostaglandin E2; NO, Nitric Oxide; FRAP, fluorescence recovery after photobleaching; ERK, extracellular signal-regulated kinases; ER, estrogen receptor; RANKL, receptor activator of nuclear factor kappa-B ligand; PI3K phosphoinositide 3- kinase; Akt, protein kinase B; CREB, cAMP response element-binding protein; INFγ, Interferon-gamma; AP1, activator protein-1; MAPK, mitogen-activated protein kinases; NF- kB, nuclear factor-κB. Corresponding Author: Dr. Swati D. Kotwal

INTRODUCTION

Osteoporosis and current treatments Osteoporosis is a skeletal disease characterized by bone loss and structural deterioration of the bone tissue, leading to an increase in bone fragility and susceptibility to fractures, most frequently in the hip, wrist and spine [1]. Various factors resulting in bone loss are age, menopause in women, smoking, alcohol excess, calcium and vitamin D deficiency, low weight and muscle mass, anticonvulsants and corticosteroid. Bone loss can also be due to co- morbid conditions such as rheumatoid arthritis [2]. Osteoporosis is a global problem in both men and women which is increasing in significance as the population of the world is growing in numbers and ageing. In old women, after menopause ageing results in deficiency of

R S. Publication, [email protected] Page 131

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 estrogen hormone, resulting in the elevation of bone resorption through osteoclastogenesis and is the most common cause of osteoporosis [3]. Worldwide, lifetime risk for osteoporotic fractures in women is 30-50% and the same in men is 15-30%. Physical exercise, dietary supplements and pharmacotherapy are usually suggested as the preventive measures. The approaches for the treatment of osteoporosis involves the supplementation of estrogen and estrogen analogues; inhibition of osteoclast proliferation and induction of osteoclast apoptosis and drugs that enhance the proliferation and differentiation of osteoblast [4]. Irrespective of the above approaches, Calcium and Vitamin D3 supplements are used as adjuvant therapy. Current therapies available for treating osteoporosis are divided into two types: one is antiresorptive agents and the other is anabolic agents. Antiresorptive agents such as bisphosphonates, estrogen, SERMs and calcitonin act to reduce bone resorption by inhibiting osteoclasts. Teriparatide, a synthetic form of parathyroid hormone, is the only anabolic agent available that acts to increase bone formation. Both antiresorptive and parathyroid hormone treatments have serious side effects [5, 6] and do not result in substantial increase in bone mass. To overcome the wide range of side effects produced by the synthetic drugs, there is increasing demands for ‘green medicine’ a healthier and safer option with less or no side effects [5]. Therapeutic effects of plant medicines are reported to be due to collective action of numerous constituents through multipathways aiming multitargets [4]. Osteoporosis being a multifactorial disorder, green medicine is expected to be especially effective. Osteoporosis is associated with inflammation and increased oxidative stress and plant based medicines that target these associated maladies along with the disease, are expected to bring desirable effects. Oxidative stress has been reported to reduce differentiation and survival of osteoblasts [7, 8, 9] and antioxidants from and fruits are known to reduce the damaging effects of reactive oxygen species (ROS) [10]. The secondary metabolites are reported to increase osteoblastic activity by increasing the expression of BMP-2, BMP-4, Runx 2 and cyclin D1. Some plant compounds also inhibit the expression of IL-6, TNFα, COX-2 and PGE2, necessary for the differentiation of osteoclasts [4]. From ancient period, many medicinal herbs (Cissus quadrangularis, Onobrychis ebenoids, Carthamus tinctorius, Ligustrum lucidum Ait) are being used for the treatment of Osteoporosis [10, 11], but very scanty information is available on the use of E. arvense.

Overview of Equisetum arvense Equisetum arvense L. (Figure 1), commonly known as horsetail, is a bushy perennial herb. The name "horsetail" is often used for the entire group, because of its resemblance to a ’s tail. The scientific name, Equisetum derives from Latin equus ("horse") + seta ("bristle"). It is the only living of the order and the Sphenopsida. It is

R S. Publication, [email protected] Page 132

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 a native of northern hemisphere, although it is widely distributed throughout Canada, USA except the southeast, Europe and Asia south to Turkey, , the Himalayas, across China (except the southeastern part), Korea and [12].

PLANT DESCRIPTION OF EQUISETUM ARVENSE

Classification:

Kingdom Plantae – Plant Superdivision Division Equisetophyta Class Sphenopsida Subclass Order Equisetales Eqisetaceae Genus Equisetum Species arvense

Morphology: The genus Equisetum consists of 30 species of rush like, conspicuously jointed, perennial herbs. Many plants in this genus prefer wet sandy soil, though some are semi aquatic and others are adapted to wet clay soils. However E. arvense prefer an acid soil. Horsetail is a strange plant with creeping, string like rootstock. Roots are present at the nodes which produce numerous hollow stems. The hollow stems are of two types, a fertile stem and a sterile stem (vegetative stem). The fertile stem appears in , is short lived and is brownish to whitish in colour. It is unbranched, thick and succulent, shorter than the vegetative stem, with larger sheaths and 10-30 cm tall. At the tip of the fertile stem is a cone like structure or (Figure 2) which contains . The strobilus withers away after spring. The sterile or vegetative stem is green, bottlebrush like, with branches at stem and contains nodes in whorls of 3 to 4. The sterile stems tend to be much taller and bushier, with the jointed segments being around one inch long with a diameter of about 1/20th of an inch. Roots may be pallid-brown, red-brown or black. Ground-level or under-ground stems are horizontal and usually rhizomatous. are reduced to small scales fused into sheaths and distributed along the stems. Sheaths of fertile stems have 8 - 12 large and pointed teeth whereas sheaths of sterile stems are green, with 10 - 12 brownish or blackish teeth [13].

PHYTOCHEMICAL PROFILE OF E. ARVENSE The commonly known phytochemical compounds in E. arvense are alkaloids, phytosterols, tannin, triterpenoids and phenolics such as flavonoids, styrylpyrones and phenolic acids [14, 15]. For medicinal purpose aerial parts, mainly sterile stems are used.

1. Sterile stem are reported to contain silicic acid and silicates (5-8%), potassium (1.8%), calcium (1.3%), aluminium, sulphur, magnesium and manganese [13, 16, 17]. 2. Styrylpyrones accumulate in of and gametophytes of E. arvense as major constitutive metabolites. In these organs, no flavonoids are detected. In green sprouts, styrylpyrone accumulation is only detected as a local response to mechanical wounding or microbial attack, and flavonoids are accumulated as major polyketide metabolites [18]. Rhizomes also contain 3'-

R S. Publication, [email protected] Page 133

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

deoxyequisetumpyrone (3, 4-hydroxy-6-(4'-hydroxy-D-styryl)-2-pyrone-3-O- -D- glucopyranoside) and 4'-Omethylequisetumpyrone (3, 4-hydroxy-6-(3'-hydroxy-4'- methoxy-Estyryl)-2-pyrone-3-O-D-glucopyranoside). Vegetative stems contain equisetumpyrone [18, 19, 20]. 3. It is reported that sterile stems contain 0.3-0.9% of total flavonoids. Various flavonoids that are present are kaempferol 3-Osophoroside-7-O-glucoside, kaempferol 3-O-(6”-O malonylglucoside)-7-O-glucoside. Kaempferol 3-O- sophoroside, quercetin3-O-glucoside, apigenin, apigenin 5-O-glucoside, luteolin, luteolin 5-O-glucoside, genkwanin 5-O-glucoside and isoquercitrin [16, 21, 22, 23, 24]. 4. Sterile stems also contain triterpenoids such as isobauerenol, taraxerol, germanicol, ursolic acid, oleanolic acid and betulinic acid [25]. 5. It is reported that fertile sprouts of E. arvense contain phenolic glycosides such as equisetumoside A, equisetumoside B and equisetumoside C [25]. Onitin and onitin- 9-O-glucoside are phenolic petrosins isolated from this plant [24]. 6. Barren sprouts of E. arvense from Asia and contain flavone 5- glucosides and their malonyl esters, whereas European sprouts are free from these compounds. Both types of sprouts contain quercetin 3-O-β-D-glucopyranoside and its malonyl ester. Quercetin 3-O-sophoroside, genkwanin 4′-O-β-D- glucopyranoside and protogenkwanin 4′-O-β-D-glucopyranoside are only found in European ones [26]. 7. Di-E-caffeoyl-meso-tartaric acid has been isolated from the methanolic extract of the barren sprouts of E. arvense as the main hydroxycinnamic acid derivative. It is a marker compound for E. arvense [27]. 8. Alkaloids such as nicotine, palustrine and palustrinine are reported from this plant [15]. 9. Sterile stems are also rich in phytosterols such as cholesterol, epicholestanol, 24- methylenecholesterol, isofucosterol (5.9%), campesterol (32.9%) and β-Sitosterol (60%) [28, 29, 30].

PHYTOCHEMICALS IN THE TREATMENT OF OSTEOPOROSIS The flavonoids and triterpenoids have been studied in vivo and in vitro for their bone conserving effects in estrogen deficiency-induced and aging-induced bone loss. Flavonoids isoquercetin, kaempferol, luteolin and apigenin are reported to prevent bone loss. The triterpenoids oleanolic acid, betulinic acid and ursolic acid are reported to stimulate osteoblast cells to increase bone formation. Isoquercetin, a quercetin glycoside, occur naturally and shows same therapeutic activity in vivo as that of quercetin (http://www.naturalmedicinejournal.com/article_content.asp?edition=1§ion=2&article=3 74). Quercetin and kaempferol have been reported in vitro to possess anabolic effect on osteoblast proliferation, differentiation and mineralisation. Both these flavonols stimulate osteoblast differentiation via ERK and ER mediated pathways [31, 32]. Quercetin and kaempferol also activate anti- inflammatory mechanism thus inhibiting osteoclast differentiation and function [33]. Quercetin is reported to inhibit RANKL - induced activation of nuclear factor kappa B and activator protein-1, a mechanism by which it inhibits osteoclast formation [34]. Inhibition of ROS generation by quercetin is implicated in its antiosteoclastic function [35]. Induction of PI3K, Akt, and CREB by Kaempferol in MC3T3-E1 line is reported as the likely cause for degeneration of osteoblasts [36]. Luteolin and apigenin are reported to stimulate osteoblast proliferation and differentiation [37]. Apigenin is reported to increase alkaline phosphatase activity and collagen content in MC3T3-E1 cell line [38]. Apigenin is also

R S. Publication, [email protected] Page 134

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 reported to inhibit osteoblast induced osteoclast function by inhibiting osteoblastic production of TNFα and interferon-gamma production [39]. Luteolin has been reported to decrease differentiation of both bone marrow mononuclear cells and Raw264.7 cells into osteoclasts and inhibits the bone resorptive activity of differentiated osteoclasts [40]. Oleanolic acid has been reported to exert an osteoprotective effect in ovariectomy induced osteoporotic rats and to stimulate the osteoblastic differentiation of bone mesenchymal stem cells in vitro [41]. Betulinic acid stimulates the differentiation and mineralisation of osteoblastic MC3T3-E1 cells. Betulinic acid has been shown to have potential to enhance osteoblastogenesis through activation of BMP/ Smad/ Runx2 and ß catenin signal pathways [42]. Ursolic acid enhances differentiation and mineralization of osteoblasts in vitro and induces the expression of osteoblast-specific genes with the activation of MAPK, NF-kB and AP1. Ursolic acid is also shown to have bone-forming activity in vivo in a mouse calvarial bone formation model [43].

BIOACTIVITIES OF EQUISETUM ARVENSE AND OSTEOPOROSIS Osteoporosis is a most common bone disorder encountered in clinical practice. With advancing age and particularly in women after menopause, it is caused by the increased activity of osteoclasts ultimately leading to osteoporosis. Age is a chief single predator for osteoporosis in women but enhanced oxidative stress is also reported as a major cause. Several studies have reported impact of oxidative stress on osteoclast differentiation as a cause of increased bone resorption [44, 45]. Furthermore in vitro and in vivo studies have suggested important role for oxidative stress in the pathogenesis of osteoporosis [8, 46]. Some of the factors involved in inflammation such as C-reactive protein, IL-6, TNF and NO also contribute to pathogenesis of osteoporosis [47, 48, 49, 50, 51]. Based on these observations secondary metabolites showing antioxidant and anti-inflammatory activity may show a reduction in the risk of osteoporosis. From ancient times, E. arvense (Horsetail) has been used for the treatment of various diseased conditions. Some of the reported activities are as follows:

As an antioxidant and free radical scavenger: Water and ethanolic extract of top (strobilus) and body portions of E. arvense (Tsukushi) shows antioxidant activity [52]. The scavenging activity of E. arvense extract and its total reducing power has been reported by FRAP assay [53].

As an anti- inflammatory agent: Hydro alcoholic extract of horsetail shows anti- inflammatory effect. It is used for conjunctivitis. Because of its anti-inflammatory action it is used for arthritis, chilblains, cystitis, gout, inflammation of the lower urinary tract, renal gravel etc. It is also used for benign enlargement of prostate gland. The tea made from horsetail is used as a gargle for mouth and gum inflammation [30].

In Bone related disorders: Costa-Rodriguez assayed the effects of hydro-methanolic extract of E. arvense on human osteoclastogenesis in vitro. The hydro-methanolic extract of E. arvense has been shown to reduce human osteoclast development and function, both in osteoclast precursor cell cultures and in co-cultures of osteoclastic and osteoblastic cells [54]. Pereira et al., studied the effect of hydro-methanolic extract on behaviour of human bone marrow cells for osteoblastic modulation in vitro. The results showed that hydro-methanolic extract of E. arvense promoted osteoblastic response while preventing risk of infection at the biomaterial/ bone interface by local delivery system [55].

R S. Publication, [email protected] Page 135

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

Equisetum arvense is reported to be useful in the treatment of osteoporosis because of its high silica content. However, only one study in 1999 has examined horsetail for osteoporosis [56]. The study, in spite of reporting improved bone density, has been criticized as poorly designed by other scientists (http://umm.edu/health/medical/altmed/herb/horsetail).

EQUISETUM ARVENSE PHYTOCHEMICALS AND TREATMENT OF OSTEOPOROSIS Equisetum arvense, a perennial herb, is a storehouse of many secondary metabolites (Table 1). E. arvense contains all the phytochemicals which are reported to be useful in the treatment of osteoporosis (refer subheading 4). In addition Equisetum arvense is rich in silica, an important mineral required for bone mineralisation. Silica is a trace element which plays an important role in our body (http/www.alive.com/articles/view/19800). Recommended daily requirement for silica has not yet been established, but according to a recent study at the Rayne Institute at St Thomas's Hospital in London, an intake of 10mg/ day was associated with significantly increased bone mineral density in pre-menopausal women and men [57]. Two main sources of silica are drinking water and plant fibres. Silica in plants is mostly found in the form of silicic acid [58] and E. arvense is an excellent source of natural silica.

Bone is a living tissue which is composed mainly of organic and inorganic matter. The greater portion of bone is type I collagen. Tissue levels of calcium have no bearing on the tissue collagen levels or health. Calcium does not play any role in the production or repair of collagen (http/ www.eidon.com/ SILICA vs CALCIUM.pdf‎). Silica is involved in early stage of bone calcification. Alone calcium supplementation cannot reverse osteoporosis [58]. Silica is necessary for proper skeleton development. Silica deficiency is a precursor to calcium deficiency and thus it leads to loss of tissue elasticity. Table 1. List of phytochemicals present in E. arvense

Silica helps in the absorption and use of calcium by the body. Many studies have shown a positive correlation between silica and bone mineral density. Various experiments conducted on chicks and rats fed on silica deficient diet showed skeletal deformities confirming the role of silica in proper skeletal development [58]. Bone matrix is a two-phase system in which the mineral phase provides the stiffness and the collagen fibres provide the ductility and ability to absorb energy (the toughness). Collagen is the most abundant protein found in the bone matrix providing flexibility to skeleton and is an important component of the connective tissues. Alterations of collagen properties are therefore likely to affect the mechanical properties of bone and increase fracture

R S. Publication, [email protected] Page 136

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738 susceptibility. A change in collagen properties alters the amount and deposition of minerals. In post menopausal osteoporosis it has been reported that at the material level, the volume fraction of mineral and the relative amounts of mature and immature collagen crosslinks are affected by the tissue turnover rates. This contributes to bone fragility [59]. It has been suggested that silicon is involved in bone formation through synthesis and stabilisation of collagen, but the underlying mechanism is not yet clear. Silica is required for the proper functioning of the enzyme prolylhydroxylase, an enzyme important for formation of collagen in bone, cartilage, and connective tissue [57]. Prolyl hydroxylation contributes to collagen stability as it induces the formation of hydrogen bonds mediated by bridging water molecules. Silica also stimulates chrondroblast (cartilage-forming cells) to deposit proteins and other structural materials on the matrix. In the light of the above discussion, E. arvense looks to be a candidate plant for the treatment of osteoporosis.

PRECAUTIONS WHILE USING EQUISETUM ARVENSE Some safety precautions are advised while using Equisetum arvense for the following reasons: 1. Chronic use of this herb causes deficiency of Vitamin B1 due to its thaiminase activity. Daily supplement of vitamin B complex is advised. 2. E. arvense contains some amount of nicotine and is not advised in combination with other substances containing nicotine. Pregnant and breastfeeding women are advised to avoid horsetail. 3. E. arvense along with other diuretics has been reported to cause hypokalemia. 4. Chronic alcohol drinkers are advised to avoid horsetail as it further decreases Vitamin B1 level in the body. 5. E. arvense in combination with lithium containing drugs is reported to cause accumulation of lithium in the body. A supervision of health expert is thus recommended while using E. arvense [12, 13].

CONCLUSION The objective of this article was to illustrate Equisetum arvense’s potential as a therapeutic agent for the treatment of osteoporosis. The traditional uses and therapeutic activity of Equisetum arvense has been established through modern testing and evaluation (preclinical and clinical) trials in different disease conditions. But its role in the treatment and prevention of osteoporosis is yet to be studied. The E. arvense contains highest percentage of silica in the whole plant kingdom and has been suggested for the treatment of Osteoporosis. In addition, E. arvense contains secondary metabolites such as quercetin, kaempferol, luteolin, apigenin, oleanolic acid, betulinic acid and ursolic acid and their role has been well documented to show anabolic activity on bone forming osteoblast cells. Together with flavonoids, triterpenoids and silica E. arvense appears to be potential candidate to prevent and treat osteoporosis. This review emphasizes the potential of E. arvense as a likely new therapeutic drug and provides the basis for future research on its application in the treatment of osteoporosis and other bone diseases.

CONFLICT OF INTEREST There is no conflict of interest.

ACKNOWLEDGEMENT Ms. S. Badole acknowledges supported by The Council of Scientific and Industrial Research, Human Resource Development Group, New Delhi (Grant No. 20-12/2009(ii) EU-IV).

R S. Publication, [email protected] Page 137

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

Authors wish to thank Dr. G. B. Shinde, Head of Department, University Department of Biochemistry, RTM Nagpur University, Nagpur for his support and encouragement throughout the completion of the review.

REFERENCES [1] Sendur, O. F., Turan, Y., Tastaban, E., & Serter, M. Antioxidant status in patients with osteoporosis: A controlled study. Joint Bone Spine, 2009, 76, 5, 514-518. [2] Javaid, M. K., & Holt, R. I. Understanding osteoporosis. Journal of Psychopharmacology (Oxford, England), 2008, 22, 38-45. [3] Rodan, G. A., Martin, T. J. Therapeutic approaches to bone diseases. Science, 2000, 289, 1508-1514. [4] Jia, M., Nie, Y., Cao, D. P., Xue, Y. Y., Wang, J. S., Zhao, L., Rahman, K., Zhang, Q. Y and Qin L. P., 2012. Potential Antiosteoporotic Agents from Plants: A Comprehensive Review. Evidence-Based Complementary and Alternative Medicine Volume, 28 pages. [5] Shirwaikar, A., Khan, S., Kamariya, H. Y., Patel, D. B. and Gajera, P. F. Medicinal Plants for the Management of Post Menopausal Osteoporosis: A Review; The Open Bone Journal2, 2010, 1-13. [6] McBane. 2011. Osteoporosis: A review of current recommendations and emerging treatment options. Available at http/formularyjournal.modernmedicine.com [7] Sahnoun, Z., Jamoussi, K., & Zeghal, K. M. Free radicals and antioxidants: human physiology, pathology and therapeutic aspects Therapie. 1997, 52(4):251-70. [8] Basu, S., Michaelsson, K., Olofsson, H., Johansson, S., & Melhus, H. Association between oxidative stress and bone mineral density. Biochem Biophys Res Commun, 2001, 288(1), 275-279 [9] Rao, A. V., & Rao, L. G. Carotenoids and human health. Pharmacological Research, 2007, 55, 3, 207-216. [10] Sharan K., Siddiqui J., Swarnkar G., Maurya R., Chattopadhyay N. Role of phytochemicals in the prevention of menopausal bone loss: evidence from in vitro and in vivo, human interventional and pharmacokinetic studies; Curr Med. Chem, 2009, 16, 1138-1157. [11] Singla C., Drabu S., Verma R., Dhiman A., Sharma A. Recent update on proficient Bone fracture revivifying herbs; IRJP 2011, 2, 3-5. [12] Asgarpanah, J., Roohi, E. Phytochemistry and pharmacological properties of Equisetum arvense L. Journal of Medicinal Plants Research 2012, 6, 3689-3693. [13] Sandhu, N. S., Kaur, S., Chopra, D. Equisetum aervens: Pharmacology and Phytochemistry- A review. Asian J. Pharmaceut. Clin. Res. 2010, 3, 146-150. [14] Mojab, F., Kamalinejad, M., Ghaderi, N., Vahidipour, H. R. Phytochemical screening of some species of Iranian plants. Iranian J. Pharmaceut. Res. 2003, 2, 77-82. [15] Cetkovic, G. S., Tumbas, V. T., Stojiljkovic, B. T. Antioxidative and antiproliferative activities of different horsetail (Equisetum arvense L.) extracts. J. Med. Food, 2010, 13, 452-459. [16] Carnet, A., Petitjean-Freytet, C., Muller, D., Lamaison, J. L. Content of major constituents of horsetails, Equisetum arvense L. Plants Med. Phytother. 1991, 25, 32- 38. [17] Holzhueter, G., Narayanan, K., Gerber, T. Structure of silica in Equisetum arvense. Anal Bioanal Chem, 2003, 376, 512-517. [18] Beckert, C., Horn, C., Schnitzler, J. P., Lehning, A., Heller, W., Veit, M. Styrylpyrone biosynthesis in Equisetum arvense. Phytochem. 1997, 44, 275-283.

R S. Publication, [email protected] Page 138

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

[19] Veit, M., Geiger, H., Wray V., Abou-Mandour, A., Rozdzinski, W., Witte, L., Strack, D., Czygan, F. C. Equisetumpyrone, a styrylpyrone glucoside in gametophytes from Equisetum arvense. Phytochem., 1993, 32, 1029-1032. [20] Veit, M., Geiger, H., Kast, B., Beckert, C., Horn, C., Kenneth, R., Wong, H. Styrylpyrone glucosides from Equisetum. Phytochem. 1995, 39, 915-917. [21] Pietta, P., Mauri, P., Bruno, A., Rava, A., Manera, E., Ceva, P. Identification of flavonoids from Ginkgo biloba L., Anthemis nobilis L. and Equisetum arvense L. by high-performance liquid chromatography with diode-array UV detection. J. Chromatog. 1991, 553, 223-231 [22] Suzuki, K., Homma, T. Isolation and chemical structure of flavonoids from horsetail (Equisetum arvense L.). J. Adv. Sci., 1997, 9, 104-105. [23] PDR for Herbal Medicines. Medical Economics Company, Inc. at Montvale, NJ, 2000, 409. [24] Oh, H., Kim, D. H., Cho, J. H., Kim, Y. C. Hepatoprotective and free radical scavenging activities of phenolic petrosins and flavonoids isolated from Equisetum arvense: J Ethnopharmacology, 2004, 95, 421-424. [25] Chang, J., Xuan, L., Xu, Y. Three new phenolic glycosides from fertile sprout of Equisetum arvense. Zhiwu Xuebao 2001, 43, 193-197. [26] Veit, M., Geiger, H., Czygan, F. C., Markham, K. R. Malonylated flavone 5-O- glucosides in the barren sprouts of Equisetum arvense. Phytochem. 1990, 29, 2555- 2560. [27] Veit, M., Strack, D., Czygan, F. C., Wray, V., Witt, L. Di-E-caffeoyl-meso-tartaric acid in the barren sprouts of Equisetum arvense. Phytochem. 1991, 30, 527-529. [28] Takatsuto, S., and Abe, H. Sterol composition of Strobilus of Equisetum arvense L. Biosci Biotech Biochem. 1992, 56, 834-835. [29] Ganeva, Y., Chanev, C., Dentchev, T. Triterpenoids and sterols from Equisetum arvense. Dokladi na Bulgarskata Akademiya na Naukite. 2001, 54, 53-56. [30] Do Monte, F. H., Dos Santos, J. G., Russi, M., Lanziotti, V. M., Leal, L. K., Cunha, G. M. Antinociceptive and antiinflammatory properties of the hydroalcoholic extract of stems from Equisetum arvense L. in mice. Pharmacol. Res. 2004, 49, 239-243. [31] Prouillet, C., Maziere, J.C., Maziere, C., Wattel, A., Brazier, M., Kamel, S. Stimulatory effect of naturally occurring flavonols quercetin and kaempferol on alkaline phosphatase activity in MG-63 human osteoblasts through ERK and estrogen receptor pathway. Biochem. Pharmacol. 2004, 67, 1307-1313. [32] Guo, A. J., Choi, R. C., Zheng, K. Y., Chen, V. P., Dong, T.T., Wang, Z. T, Vollmer, G., Lau, D. T and K. Wah-keung Tsim. Kaempferol as a flavonoid induces osteoblastic differentiation via estrogen receptor signaling. Chinese Medicine, 2012, 7-10 [33] Pang, J.L., Ricupero, D.A., Huang, S., Fatma, N., Singh, D.P., Romero, J.R., Chattopadhyay, N. Differential activity of kaempferol and quercetin in attenuating tumor necrosis factor receptor family signaling in bone cells. Biochem. Pharmacol., 2006.,71, 818-826. [34] Wattel, A., Kamel, S., Prouillet, C., Petit, J.P., Lorget, F., Offord, E., Brazier, M. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a smechanism involving NF kappa B and AP-1. J. Cell. Biochem., 2004, 92, 285-295. [35] Bax, B.E., Alam, A.S., Banerji, B., Bax, C.M., Bevis, P.J., Stevens, C.R., Moonga, B.S., Blake, D.R., Zaidi, M. Stimulation of osteoclastic bone resorption by hydrogen peroxide. Biochem. Biophys. Res. Commun., 1992, 183, 1153-1158. [36] Choi, E. M. Kaempferol protects MC3T3-E1 cells through antioxidant effect and regulation of mitochondrial function. Food and Chemical Toxicology: An

R S. Publication, [email protected] Page 139

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

International Journal Published for the British Industrial Biological Research Association, 2011, 49, 8, 1800-1805. [37] Choi, E.H., Ok, H.E., Yoon, Y., Magnuson, B.A., Kim, M.K., Chun, H.S. Protective effect of anthocyanin-rich extract from bilberry (Vaccinium myrtillus L.) against myelotoxicity induced by 5-fluorouracil. Biofactors, 2007, 29, 55-65. [38] Choi, E.M. Apigenin increases osteoblastic differentiation and inhibits tumor necrosis factor-alpha-induced production of interleukin-6 and nitric oxide in osteoblastic MC3T3-E1 cells. Pharmazie., 2007, 62, 216-220. [39] Bandyopadhyay, S., Lion, J.M., Mentaverri, R., Ricupero, D.A., Kamel, S., Romero, J.R., Chattopadhyay, N. Attenuation of osteoclastogenesis and osteoclast function by apigenin. Biochem. Pharmacol., 2006, 72, 184-197. [40] Kim, T. H., Jung, J. W., Ha, B. G., Hong, J. M., Park, E. K., Kim, H. J., et al. The effects of luteolin on osteoclast differentiation function in vitro and ovariectomy- induced bone loss. The Journal of Nutritional Biochemistry, 2011, 22(1), 8-15. [41] Bian, Q., Liu, S. F., Huang, J, H., Yang, Z., Tang, D. Z., Zhou, Q., Ning, Y., Zhao, Y. J., Lu, S., Shen, Z. Y., Wang, Y. J. Oleanolic acid exerts an osteoprotective effect in ovariectomy-induced osteoporotic rats and stimulates the osteoblastic differentiation of bone mesenchymal stem cells in vitro. Menopause, 2012, 19, 2, 225-233. [42] Chen, Y., Chang, Y. H., Wei, B. L., Huang, Y.L., and Wen-Fei Chiou, W. F. Betulinic Acid Stimulates the Differentiation and Mineralization of Osteoblastic MC3T3-E1 Cells: Involvement of BMP/Runx2 and β-Catenin Signals. J. Agric. Food Chem., 2010, 58, 11, 6643–6649. [43] Lee, S. U., Park, S. J., Kwak, H. B., Oh, J., Min, Y. K., Kim, S. H. Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo. Pharmacological Research, 2008, 58, 5–6, 290-296. [44] Mody, N., Parhami, F., Sarafian, T. A., & Demer, L. L. Oxidative stress modulates osteoblastic differentiation of vascular and bone cells. Free Radical Biology & Medicine, 2001, 31, 4, 509-519. [45] Lean J. M., Davies J. T., Fuller K., Jagger C. J., Kirstein B., Partington G. A., et al., A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest, 2003, 112, 6, 915-923. [46] Maggio, D., Barabani, M., Pierandrei, M., Polidori, M. C., Catani, M., Mecocci, P., et al. Marked decrease in plasma antioxidants in aged osteoporotic women: Results of a cross-sectional study. J Clin Endocrinol Metab, 2003, 88, 4, 1523-1527. [47] Scheidt-Nave, C., Bismar, H., Leidig-Bruckner, G., Woitge, H., Seibel, M. J., Ziegler, R., Pfeilschifter, J. Serum interleukin 6 is a major predictor of bone loss in women specific to the first decade post menopause. J Clin Endocrinol Metab, 2001, 86:2032- 42. [48] Ganesan, K., Teklehaimanot, S., Tran, T. H., Asuncion, M., Norris, K. Relationship of C-reactive protein and bone mineral density in community-dwelling elderly females. J Natl Med Assoc, 2005, 97:329-33. [49] Ginaldi, L., Benedetto, C. and De Martinis, M. Osteoporosis, Inflammation And Ageing Immunity & Ageing 2005, 2:14 [50] Koh, J. M., Kang, Y. H., Jung, C. H., Bae, S., Kim, D. J., Chung, Y. E., Kim, G. S. Higher circulating hsCRP levels are associated with lower bone mineral density in healthy pre-and postmenopausal women: evidence for a link between systemic inflammation and osteoporosis. Osteoporosis Int, doi:. 10.1007/s00198-005- 1840-5, 2005. [51] Moffett, S. P., Zmuda, J. M., Oakley, J. I., Beck, T. J., Cauley, J. A., Stone, K. L., Lui, L. Y., Ensrud, K. E., Hillier, T. A., Hochberg, M. C., Morin, P., Peltz, G.,

R S. Publication, [email protected] Page 140

International Journal of Pharmaceutical Science and Health Care Issue 4, Vol 1. February 2014 Available online on http://www.rspublication.com/ijphc/index.html ISSN 2249 – 5738

Greene, D., Cummings, S. R. Tumor necrosis factor-alpha polymorphism, bone strength phenotypes, and the risk of fracture in older women. J Clin Endocrinol Metab, 2005, 90:3491-7. [52] Nagai, T., Myoda, T., Nagashima, T. Antioxidative activities of water extract and ethanol extract from field horsetail (tsukushi) Equisetum arvense L, Food chem 2005, 91, 389-394. [53] Stajner D., Popovic, B. M., Canadanovic, J., Boza, P. Free radical scavenging activity of three Equisetum species from Fruska Gora Mountain. Fitoterapia 2006, 77, 601- 604. [54] Costa-Rodrigues J., Carmo C. S., Silva J., Fernandes M. Inhibition of human in vitro osteoclastogenesis by Equisetum arvense. Cell Proliferation, 2012, 45, 566-576. [55] Pereira, B. C., Gomes, S. P., Almeida Palmas, R., Vieira, L., Ferraz, M., Lopes, M., Fernandes, M. Equisetum arvense hydromethanolic extracts in bone regeneration: in vitro osteoblastic modulation and antibacterial activity. Cell Proliferation, 2012, 45, 386-396. [56] Corletto F. Female climacteric osteoporosis therapy with titrated horsetail (E. arvense) extract plus calcium (Osteosil calcium): randomised double blind study. Miner. Ostoped Traumatol; 1999, 50: 201-206. [57] Jugdaohsingh R. Silicon and Bone Health. J Nutr Health Aging. 2007, 11, 99–110. [58] Seaborn, D. C., and Nielsen, H. F., 1993. Silicon: A nutritional beneficence for bones, brains and blood vessels. Nutrition today. [59] Carrin-Viguet, S., Garnero, P., Delmas, P. D. The role of Collagen. Osteoporos Int 2006, 17, 319–336.

R S. Publication, [email protected] Page 141