€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ZHONGYAO TONGBAO***** Tang ZX Zeng F Zeng Y Li D Chen J [PRELIMINARY STUDY ON THE ANTITUMOR ACTIVITIES OF AGRIMONIA PILOSA LEDEB] In: Zhongyao Tongbao (1981) 6(6):34 (Published in Chinese) An aqueous extract of Agrimonia pilosa was used on numerous transplantable experimental tumors. The following lines were included: murine sarcoma S180, uterine cervix carcinoma U14, brain tumor B22, Ehrlich ascitic carcinoma, melanoma B16, and rat Walker 256 carcinoma. The extract exhibited varying degrees of inhibitory effects (36.2-65.9%) on all the above tumor lines. (no Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****AMERICAN JOURNAL OF CHINESE MEDICINE***** Wang JP Hsu MF Teng CM Antihemostatic effect of Hsien-Ho-T'sao (Agrimonia pilosa). In: Am J Chin Med (1984 Summer) 12(1-4):116-23 ISSN: 0192-415X Bleeding time in rats was markedly prolonged after the administration of the water extract of Hsien-Ho-T'sao. This antihemostatic effect was more marked in the group of i.p. injection of the drug than in the group of p.o. administration for 2 or 7 consecutive days. Blood coagulation studies showed that plasma prothrombin time, activated partial thromboplastin time and stypven time were prolonged, while thrombin time and fibrinogen level were not changed. The thromboelastographic recording showed that reaction time was prolonged and maximal elasticity of clot was decreased. In addition, ADP- and collagen- induced aggregations of platelet-rich plasma were suppressed. In conclusion, the prolongation of the bleeding time might be due to both anticoagulant and antiplatelet action of the drug. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Hsu MF Young JH Wang JP Teng CM Effect of hsien-ho-t'sao (Agrimonia pilosa) on experimental thrombosis in mice. In: Am J Chin Med (1987) 15(1-2):43-51 ISSN: 0192-415X The water extract of Hsien-Ho-T'sao (HHT) prolonged the tail bleeding time in conscious mice. This antihemostatic effect was dose-dependent and exhibited a biphasic pattern; i.e. its activity declined at doses higher than 0.5 mg/kg. the prolonged bleeding time persisted for at least 12 hr and maximal effect was observed at 3 hr after the oral administration of HHT 500 mg/kg. HHT was effective in preventing ADP- induced acute pulmonary thromboembolic death in mice, while aspirin and indomethacin had no effect on this model. HHT, like aspirin and indomethacin, also reduced the mortality in collagen- and sodium arachidonate-induced thromboembolic death. All three drugs caused no significant protection in endotoxin shock. HHT was found to suppress platelet aggregation markedly, but little effect on blood coagulation. In conclusion, HHT was proved to be effective in the treatment of acute pulmonary thromboembolism, and this effect was mainly due to its antiplatelet action. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Wang JP Hsu MF Teng CM Antiplatelet effect of hsien-ho-t'sao (Agrimonia pilosa). In: Am J Chin Med (1985) 13(1-4):109-18 ISSN: 0192-415X The water extract of Hsien-Ho-T'sao (HHT) produced a dose-dependent inhibition on collagen-induced aggregation of platelet-rich plasma (PRP). The IC50 was about 3.5 mg/ml. In addition, HHT inhibited also the aggregation induced by ADP, A23187 or arachidonate in PRP. Greater inhibition was observed in the preparation of washed platelets. Increase of the calcium concentration in medium could not overcome the inhibitory effect of HHT. ATP release from platelets induced by collagen or A23187 was inhibited by HHT. In the presence of EDTA, ATP release caused by thrombin or A23187 was also inhibited by HHT. Malondialdehyde and thromboxane B2 formation was greatly inhibited by HHT in platelets challenged by collagen and thrombin. In arachidonate-stimulated platelets, thromboxane B2, but not malondialdehyde formation was inhibited. HHT showed more marked inhibition on aggregation in the presence of indomethacin, creatine phosphate/creatine phosphokinase or a combination of both. Hydrogen peroxide-induced hemolysis was marked reduced by HHT. It was concluded that HHT might have some membrane-active properties which interfered with the activation of phospholipase A2. Registry Numbers: 506-32-1 (Arachidonic Acid) 52665-69-7 (Calcimycin) 53-86-1 (Indomethacin) 542-78-9 (Malondialdehyde) 54397-85-2 (Thromboxane B2) 56-65-5 (Adenosine Triphosphate) 7440-70-2 (Calcium) 9007-34-5 (Collagen) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****ANTICANCER RESEARCH***** Murayama T Kishi N Koshiura R Takagi K Furukawa T Miyamoto K Agrimoniin, an antitumor tannin of Agrimonia pilosa Ledeb., induces interleukin-1. In: Anticancer Res (1992 Sep-Oct) 12(5):1471-4 ISSN: 0250-7005 The induction of interleukin-1 (IL-1) by agrimoniin, a tannin of Agrimonia pilosa Ledeb., in human peripheral blood mononuclear cells (PBMC) in vitro and in mouse adherent peritoneal exudate cells (PEC) in vivo was studied. A significant amount of IL-1 beta in the culture supernatant of the human PBMC stimulated with agrimoniin was detected with an enzyme-linked immunoadherent assay. Agrimoniin induced IL-1 beta secretion dose- and time-dependently. The adherent PEC from mice intraperitoneally injected with agrimoniin (10 mg/kg) also secreted IL-1 4 days later. These results suggest that agrimoniin, a plant tannin, is a novel cytokine inducer. Registry Numbers: 82203-01-8 (agrimoniin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****CANCER IMMUNOLOGY, IMMUNOTHERAPY***** Miyamoto K Kishi N Murayama T Furukawa T Koshiura R Induction of cytotoxicity of peritoneal exudate cells by agrimoniin, a novel immunomodulatory tannin of Agrimonia pilosa Ledeb. In: Cancer Immunol Immunother (1988) 27(1):59-62 ISSN: 0340-7004 The cytotoxic activities of the PEC after an i.p. injection of agrimoniin, a tannin contained in Agrimonia pilosa Ledeb. were studied. The plastic nonadherent PEC had significantly higher NK cell activity than the untreated control, and the adherent PEC were cytostatic toward MM2 and MH134 cells. The adherent PEC did not cause tumor cell lysis by themselves, but were cytolytic against MM2 cells in the presence of anti-MM2 sera. In the course of these effects of PEC after the i.p. injection of agrimoniin, the augmentation of NK cell activity was the earliest reaction, reaching a peak at 2 days after the injection; then, cytostatic activity increased. The induction of antibody-dependent cell lytic activity was a later reaction, which reached a peak at 6 days after the injection. Registry Numbers: 82203-01-8 (agrimoniin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ **CHUNG-KUO CHUNG YAO TSA CHIH CHINA JOURNAL OF CHINESE MATERIA MEDICA* Lin XY Li XL Yang Y [Determination of trace elements in several hemostatic medicinal plants and their boiling water extracts] In: Chung Kuo Chung Yao Tsa Chih (1993 Apr) 18(4):223-4, 254-5 ISSN: 1001-5302 (Published in Chinese) The experimental results indicate that the amounts of Cu, Zn, Fe and Mn in Rubia cordifolia and Agrimonia pilosa var. japonica are very small in boiling water extracts (only 6%). But after digestion they may rise to 30%. It was found that the amounts of four trace elements decreased with the increase of extracting time, but the ratios of Mn/Zn and Zn/Cu were almost the same. Registry Numbers: 7439-89-6 (Iron) 7439-96-5 (Manganese) 7440-50-8 (Copper) 7440-66-6 (Zinc) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****DIABETOLOGIA***** Swanston-Flatt SK Day C Bailey CJ Flatt PR Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. In: Diabetologia (1990 Aug) 33(8):462-4 ISSN: 0012-186X The effects on glucose homeostasis of eleven plants used as traditional treatments for diabetes mellitus were evaluated in normal and streptozotocin diabetic mice. Dried leaves of agrimony (Agrimonia eupatoria), alfalfa (Medicago sativa), blackberry (Rubus fructicosus), celandine (Chelidonium majus), eucalyptus (Eucalyptus globulus), lady's mantle (Alchemilla vulgaris), and lily of the valley (Convallaria majalis); seeds of coriander (Coriandrum sativum); dried berries of juniper (Juniperus communis); bulbs of garlic (Allium sativum) and roots of liquorice (Glycyrhizza glabra) were studied. Each plant material was supplied in the diet (6.25% by weight) and some plants were additionally supplied as decoctions or infusions (1 g/400 ml) in place of drinking water to coincide with the traditional method of preparation. Food and fluid intake, body weight gain, plasma glucose and insulin concentrations in normal mice were not altered by 12 days of treatment with any of the plants. After administration of streptozotocin (200 mg/kg i.p.) on day 12 the development of hyperphagia, polydipsia, body weight loss, hyperglycaemia and hypoinsulinaemia were not affected by blackberry, celandine, lady's mantle or lily of the valley. Garlic and liquorice reduced the hyperphagia and polydipsia but did not significantly alter the hyperglycaemia or hypoinsulinaemia. Treatment with agrimony, alfalfa, coriander, eucalyptus and juniper reduced the level of hyperglycaemia during the development of streptozotocin diabetes. This was associated with reduced polydipsia (except coriander) and a reduced rate of body weight loss (except agrimony). Alfalfa initially countered the hypoinsulinaemic effect of streptozotocin, but the other treatments did not affect the fall in plasma insulin. The results suggest that certain traditional plant treatments for diabetes, namely agrimony, alfalfa, coriander, eucalyptus and juniper, can retard the development of streptozotocin diabetes in mice. €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****JAPANESE JOURNAL OF PHARMACOLOGY***** Miyamoto K Kishi N Koshiura R Antitumor effect of agrimoniin, a tannin of Agrimonia pilosa Ledeb., on transplantable rodent tumors. In: Jpn J Pharmacol (1987 Feb) 43(2):187-95 ISSN: 0021-5198 The effect of agrimoniin, a tannin contained in Agrimonia pilosa LEDEB., on ascites type and solid type rodent tumors was investigated. When agrimoniin was intraperitoneally (i.p.) administered at dosages over 10 mg/kg before or after the MM2 cell i.p. inoculation, this tannin almost completely rejected the tumor growth in the mice. This tannin prolonged the life span of mice bearing MM2 or cured by the intravenous or per oral pre- or postmedication. Agrimoniin also inhibited the growth of MH134 and Meth-A solid type tumors. Agrimoniin showed strong cytotoxicity on MM2 cells in vitro, but the activity was diminished to about 4% of the initial activity by the addition of fetal calf serum to the culture. On the other hand, i.p. injection of agrimoniin increased the number of peripheral white blood cells and the ratio of monocytes. On the 4th day after the i.p. injection of the tannin, cytotoxic adherent peritoneal exudate cells were also increased. The spleen of the mice was enlarged, and the spleen cells possessed the capacity to take up 3H-thymidine. Agrimoniin showed weak direct migration activity against spleen cells from non-treated mice. These results indicate that agrimoniin is a potent antitumor tannin and suggest that the antitumor effect may be due to this tannin enhancing the immune response of the host animals through the actions on tumor cells and some immunocytes. Registry Numbers: 50-89-5 (Thymidine) 82203-01-8 (agrimoniin) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Koshiura R Miyamoto K Ikeya Y Taguchi H Antitumor activity of methanol extract from roots of Agrimonia pilosa Ledeb. In: Jpn J Pharmacol (1985 May) 38(1):9-16 ISSN: 0021-5198 To evaluate the antitumor activity of Agrimonia pilosa LEDEB., the effects of the methanol extract from roots of the plant (AP-M) on several transplantable rodent tumors were investigated. AP-M significantly prolonged the life span of S180-, Meth-A fibrosarcoma- and MM-2 mammary carcinoma-bearing mice by intraperitoneal (i.p.) pre- or postmedication. AP-M also inhibited the growth of S-180 solid type tumor. On the other hand, the prolongation of life span induced by AP-M on S-180 ascites type tumor-bearing mice was markedly minimized or abolished by the pretreatment of cyclophosphamide. AP-M showed considerably strong cytotoxicity on MM-2 cells in vitro, but the effect was diminished to one-tenth by the addition of serum to the culture. Against the host animals, the peripheral white blood cells in mice were significantly increased from 2 to 5 days after the i.p. injection of AP-M. On 4th day after the injection of AP-M, the peritoneal exudate cells which possessed the cytotoxic activity on MM- 2 cells in vitro were also increased to about 5-fold those in the non- treated control. The spleen of the mice was enlarged, and the spleen cells possessed the capacity to uptake 3H-thymidine. However, AP-M did not show direct migration activity like other mitogens against spleen cells from non-treated mice. These results indicate that the roots of Agrimonia pilosa contain some antitumor constituents, and possible mechanisms of the antitumor activity may be some host- mediated actions and direct cytotoxicity. Registry Numbers: 50-89-5 (Thymidine) 67-56-1 (Alcohol, Methyl) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****MUTAGENESIS***** Horikawa K Mohri T Tanaka Y Tokiwa H Moderate inhibition of mutagenicity and carcinogenicity of benzo[a]pyrene, 1,6-dinitropyrene and 3,9-dinitrofluoranthene by Chinese medicinal herbs. In: Mutagenesis (1994 Nov) 9(6):523-6 ISSN: 0267-8357 The activity of six Chinese medicinal herbs against the environmental mutagens and carcinogens benzo[a]pyrene (B[a]P), 1,6-dinitropyrene (1,6-diNP) and 3,9-dinitrofluoranthene (3,9-diNF) was determined. Samples of Prunella spica, Rheum palmatum, Polygonum multiflorum, Agrimonia pilosa, Ephedra sinica and Teitoutou were tested in an in vitro system. Antimutagenic activity against B[a]P was marked in the presence of extracts (boiled for 2 h in a water bath) whereas that against 1,6-diNP and 3,9-diNF varied from 20 to 86%. The differences in inhibition might be due to inactivation of metabolic enzymes. An extract of P. multiflorum was divided into ether, ethyl acetate and water soluble fractions, which were tested for antimutagenic activity against B[a]P. The antimutagenic action of the ethyl acetate soluble fraction was substantial and dose-dependent. Tannins and related compounds were the major components of the extract, of which epigallocatechin, epigallocatechin gallate, epicatechin gallate and tannic acid strongly inhibited the mutagenicity of B[a]P (2.5 micrograms/plate) in Salmonella typhimurium TA98 with S9 mix. To confirm the results of the in vitro test system, F344/DuCrj male rats were given a subcutaneous injection of B[a]P. Thereafter, they received water extracts of the six Chinese medicinal herbs for 50 weeks and were examined for tumors. The P. multiflorum extract significantly reduced the tumor incidence. Registry Numbers: 22506-53-2 (3,9-dinitrofluoranthene) 42397-64-8 (1,6-dinitropyrene) 50-32-8 (Benzo(a)pyrene) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAKUGAKU ZASSHI. JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN***** Koshiura R Miyamoto K Takada Y Kiriyama N [STUDIES ON THE CONSTITUENTS OF AGRIMONIA PILOSA LEDEB. I. BIOLOGICAL ACTIVITIES OF THE ACIDIC FRACTION OF THE ROOTS THAT IS SOLUBLE IN N- HEXANE] In: Yakugaku Zasshi (1980) 100(11):1167-1170 ISSN: 0031-6903 (Published in Japanese) Interesting biological activity was observed in fractions of an extract of Agrimonia pilosa LEDEB roots. These fractions were different from already-established components of A pilosa. An extraction of dried A pilosa roots collected from the Katsuyama-shi region of Fukui Prefecture was performed, and cytotoxic and antitumor activities of the various fractions were assessed in HeLa cells (colony forming method) and Ehrlich ascites carcinoma cells (in vitro- in vivo method). Fraction III inhibited HeLa cell colony formation 50% at concentrations of 12 ug/ml (IC50), prolonged the life of Ehrlich ascites carcinoma-bearing mice 32% more than controls at a concentration of 12.5 ug/ml, and prolonged the survival of 4/5 Ehrlich ascites carcinoma-bearing ddy mice greater than 60 days. Fraction VIII had an IC50 towards HeLa colony formation of 1.5 ug/ml and showed hemo-agglutinability and hemolytic action in the absence of protein in HeLa cells. (18 Refs) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ *****YAO HSUEH HSUEH PAO [ACTA PHARMACEUTICA SINICA]***** Pei YH Li X Zhu TR [Studies on the structure of a new ellagic acid glycoside from the root-sprouts of Agrimonia pilosa Ledeb] In: Yao Hsueh Hsueh Pao (1990) 25(10):798-800 ISSN: 0513-4870 (Published in Chinese) Four compounds were isolated from the root-sprouts of Agrimonia pilosa Ledeb. On the basis of physico-chemical properties, spectroscopy (UV, IR, NMR, MS) and chemical degradation, a new compound was elucidated as ellagic acid-4-O-beta-D-xylopyranoside (XV), and three known compounds were identified as agrimonolide (XIII), tormentic acid (XIV), and ellagic acid (XVI). Registry Numbers: 139163-18-1 (ellagic acid 4-O-xylopyranoside) 21499-24-1 (agrimonolide) 476-66-4 (Ellagic Acid) 53155-25-2 (euscaphic acid) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pei YH Li X Zhu TR Wu LJ [Studies on the structure of a new flavanonol glucoside of the root- sprouts of Agrimonia pilosa Ledeb] In: Yao Hsueh Hsueh Pao (1990) 25(4):267-70 ISSN: 0513-4870 (Published in Chinese) Three compounds were isolated from benzene and acetone extracts of the root-sprouts of Agrimonia pilosa Ledeb. On the basis of physicochemical properties, spectroscopy (UV, IR, NMR, MS, CD, GC) and chemical degradation, two known compounds were identified as palmitic acid (VIII) and daucosterol (IX), one new compound was elucidated as (2S,3S)-(-)-taxifolin-3-O-beta-D-glucopyranoside (X). Registry Numbers: 117-39-5 (Quercetin) 129212-92-6 (taxifolin-3-glucopyranoside) 474-58-8 (lyoniside) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pei YH Li X Zhu TR [Studies on the structure of a new isocoumarin glucoside of the root sprouts of Agrimonia pilosa Ledeb] In: Yao Hsueh Hsueh Pao (1989) 24(11):837-40 ISSN: 0513-4870 (Published in Chinese) Trans-p-hydroxycinnamic esters VI and an isocoumarin glucoside VII were isolated from the benzene and acetone extracts of the root sprouts of Agrimonia pilosa Ledeb. On the basis of physicochemical properties, spectral data (UV, IR, NMR, MS, CI-MS-MS), GC and chemical degradation, VI was elucidated as trans-p-hybroxycinnamic esters of n-C22, n-C24-32, n-C34, alcohols, VII was elucidated as agrimonolide-6-Q-beta-D-glucopyranoside. VII and trans-p- hydroxycinnamic esters of n-C29-32 and n-C34 alcohols are new compounds. Registry Numbers: 126223-29-8 (agrimonolide-6-O-glucopyranoside) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€ Pei YH Li X Zhu TR [Studies on the chemical constituents from the root-sprouts of Agrimonia pilosa Ledeb] In: Yao Hsueh Hsueh Pao (1989) 24(6):431-7 ISSN: 0513-4870 (Published in Chinese) Five compounds were isolated from the petroleum ether extract of the root-sprouts of Agrimonia pilosa Ledob. A new compound, (R)-(-)- agrimol B (III), was elucidated by means of physical and chemical properties, spectroscopy (MS, IR, PMR, UV) and total synthesis. Four known compounds were identified as agrimophol (I), n-nonacosane (II), beta-sitosterol (IV) and pseudo-aspidin (V), the last one being previously known only as a synthetic entity. (S)-(+)-Agrimol B also was synthesized. Registry Numbers: 55576-66-4 (agrimol B) €€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€€