本文選題：山茱萸 + 化學(xué)成分��； 參考：《北京中醫(yī)藥大學(xué)》2017年碩士論文

【摘要】：山茱萸為山茱萸科(Cornaceae)植物山茱萸Cornus officinalis Sieb.et Zucc.的干燥成熟果肉,主產(chǎn)于陜西、山西、河南等省,是我國傳統(tǒng)的名貴滋補中藥材。其藥用歷史已有兩千余年,始載于《神農(nóng)本草經(jīng)》"治心下邪氣寒熱,溫中逐寒濕痹,去三蟲,久服輕身",其性酸、澀,微溫,歸肝、腎經(jīng),具有補益肝腎和澀精固脫之功效。山茱萸是一些經(jīng)典中藥名方的主藥,如六味地黃丸、金匱腎氣丸、左歸丸等。研究表明山茱萸的化學(xué)成分主要為環(huán)烯醚萜類、鞣質(zhì)類、黃酮類、三萜類和苯丙素類等�，F(xiàn)代藥理學(xué)研究表明山茱萸在抗炎、糖尿病的防治、心腦血管的保護、神經(jīng)保護、抗腫瘤、抗氧化和抗衰老等方面均表現(xiàn)出較好的活性。雖然山茱萸含有多種藥理活性,但其研究多集中于粗提物水平,而單體化合物少有報道。為了更好的闡明山茱萸的藥效物質(zhì)基礎(chǔ),對其化學(xué)成分進行系統(tǒng)的研究具有十分重要的意義。本論文對山茱萸水提物的化學(xué)成分進行了較系統(tǒng)地分離和結(jié)構(gòu)鑒定,并且對分離到的單體化合物進行了初步的抗炎和神經(jīng)保護作用的評價,為山茱萸的進一步開發(fā)利用提供了科學(xué)依據(jù)。根據(jù)環(huán)烯醚萜類化合物的最大紫外吸收在230 nm處特點,采用化學(xué)導(dǎo)向分離的思路,運用硅膠柱色譜、ODS柱色譜、SephadexLH-20柱色譜和制備高效液相色譜等方法從山茱萸中分離純化得到80個化合物,根據(jù)UV、IR、MS、HRESIMS、1DNMR、2DNMR、CD、ECD等技術(shù)方法,鑒定了其中72個化合物的結(jié)構(gòu),包括41個環(huán)烯醚萜苷類化合物、3個單萜類化合物、5個黃酮類化合物、13個木脂素類化合物以及10個其它類型化合物(化合物名稱見下表),它們分別為:cornuside A(1*),cornuside B(2*),cornuside C(3*),cornuside D(4*),cornuside E(5*),cornuside F(6*),cornuside G(7*),cornuside H(8*),cornuside I(9*),cornuside J(10*),cornuside K(11*),cornuside L(12*),cornuside M(13*),cornuside N(14*),cornuside O(15*),cornuside P(16*),cornuside Q(17*),cornusfuroside A(18*),cornusfuroside B(19*),cornusfuroside C(20*),cornusfuroside D(21*),6'-O-acetyl-7α-O-ethyl(22*),6-O-acetyl-7β-O-ethyl(23*),cornusglucoside A(24*),comusglucoside B(25*),comusglucoside C(26*),comusglucoside D(27*),cornusglucoside E(28*),cornusglucoside F(29*),comusglucoside G(30*),cornusglucoside H(31*),williamsoside D(32),loganin(33),8-epiloganin(34),7β-O-morroniside(35),7α-O-morroniside(36),7β-O-methyl morroniside(37),7α-O-methyl morroniside(38),7β-O-ethyl morroniside(39),7α-O-ethyl morroniside(40),sweroside(41),sarracenin(42),sachalinoide B(43),(4α)-3-(5,5-dimethyltetrahydrofuranyl)-1-buten-3-ol 3-O-β-D-glucopyranoside(44),apigenin(45),chrysoderol(46),luteolin(47),quercetin(48),dihydroapigenin(49)3,4,3',4'-tetrahydroxy-δ-truxinate(50),(-)-isolariciresinol 3α-O-β-D-glucopyranoside(51),(+)-isolariciresinol 3α-O-/β-D-glucopyranoside(52),(+)-pinoresinol(53),(+)-epipinoresinol(54),syringaresinol(55),(-)-episyringaresinol(56),(-)-medioresinol(57),(7S,8R)-urolignoside(58),glochidioboside(59),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-β-D-glucopyranoside(60),(-)-secoisolariciresinol-9'-O-β-D-glucopyranoside(61),4-0-(6'-O-galloyl-β-D-glucopyranosyl)-cis-pcoumaric acid(62),5-(1 '-hydroxyethyl ethylenediamine)-methyl nicotinate(63),cirsiumaldehyde(64),5-hydroxymethylfurfural(65),p-Hydroxybenzoic acid(66),ethyl gallate(67),syringate(68),p-coumaric acid(69),caffeic acid(70),caffeic acid methyl ester(71),p-methoxycinnamicacid(72)。其中化合物 1～31 為新化合物,化合物42～47,49～～64和72為首次從山茱萸屬植物中分離得到。基于熒光素酶報告基因技術(shù)研究化合物1～15和32～41對STAT3通路的影響,評價其抗炎活性。實驗結(jié)果顯示化合物3,12,33,35,36對STAT3通路表現(xiàn)出明顯的抑制活性且未表現(xiàn)出細胞毒性,構(gòu)效關(guān)系研究表明:a.化合物的C-7"為β構(gòu)型且與葡萄糖的C-3'脫水縮合形成醚鍵時,對STAT3通路表現(xiàn)出明顯的抑制活性;b.化合物的C-7"為α構(gòu)型且與葡萄糖的C-6'脫水縮合形成醚鍵時對STAT3通路表現(xiàn)出明顯的抑制活性;c.馬錢苷和7α,β-莫諾苷對STAT3通路表現(xiàn)出明顯的抑制活性。采用脂多糖(LPS)誘導(dǎo)小鼠腹腔巨噬細胞(RAW264.7)模型,采用ELISA試劑法檢測化合物對細胞分泌的TNF-α、IL-6的抑制作用,評價化合物32～41的抗炎活性。實驗結(jié)果表明化合物33對炎性因子TNF-α分泌的抑制作用超過50%,其余化合物未顯示出抑制效果。此外,還對化合物1～15和32～41進行了 PC12細胞缺氧缺糖損傷保護作用的篩選。實驗結(jié)果表明篩選的25個化合物中,化合物1和3與OGD/R相比,細胞存活率提高,說明化合物1和3對OGD/R損傷的PC12細胞物有一定的保護作用。
[Abstract]:The Cornus officinalis is the dry mature pulp of the Cornaceae plant of Cornus officinalis (Cornaceae) Cornus officinalis Sieb.et Zucc.. It mainly produced in the province of Shaanxi, Shanxi, Henan and other provinces. It has been used as the traditional medicinal herbs in China. Its medicinal history has been used for more than two thousand years. "Light body", its sexual acid, astringent, micro temperature, return to the liver, kidney meridian, with the effect of liver and kidney and astringent essence. Cornus is the main medicine of some classic Chinese medicine, such as six flavored Rehmannia pills, Jingui kidney qi pill, Zuo GUI pill and so on. The chemical composition of the fruit is mainly composed of eidolene, tannins, flavonoids, three terpenoids and phenylpropanoids. The study shows that the Fructus Corni showed good activity in the aspects of anti inflammation, prevention and control of diabetes, protection of cardiovascular and cerebrovascular, neuroprotection, antitumor, antioxidation and anti aging. Although the Fructus cornel contains a variety of pharmacological activities, its research is mostly concentrated on the level of crude extract, but few of the monomers are reported. It is of great significance to systematically study the chemical components of Cornus officinalis. This paper systematically separates and identifies the chemical constituents of the aqueous extracts of Cornus officinalis, and the preliminary evaluation of the anti-inflammatory and neuroprotective effects of the isolated monomers, for the further opening of Cornus officinalis. According to the characteristics of the maximum UV absorption of the iridoid compounds at 230 nm, 80 compounds were isolated and purified from the Fructus Corni by silica gel column chromatography, ODS column chromatography, SephadexLH-20 column chromatography and preparation high performance liquid chromatography, according to the characteristics of the maximum UV absorption of the iridoid compounds, and 80 compounds were isolated and purified from the Cornus officinalis by means of silica gel column chromatography, SephadexLH-20 column chromatography and preparation of high performance liquid chromatography. According to UV, IR, MS, HRESIMS, 1DNMR, 2DNMR, CD, ECD and other technical methods, identified the structure of 72 of these compounds, including 41 iridoid terpenoids, 3 monoterpenes, 5 flavonoids, 13 lignans and 10 other types of compounds (the compounds are named as cornuside A (1*), cornuside B (2*), cornusid, respectively. E C (3*), cornuside D (4*), cornuside E (5*), cornuside F (6*). C (20*), cornusfuroside D (21*), 6'-O-acetyl-7 alpha -O-ethyl (22*), 6-O-acetyl-7 beta -O-ethyl (23*). -epiloganin (34), 7 beta -O-morroniside (35), 7 alpha -O-morroniside (36), 7 beta -O-methyl morroniside (37), 7 alpha -O-methyl morroniside (38), 7 beta -O-ethyl morroniside (39), 7 alpha -O-ethyl morroniside (40), sweroside. (44), apigenin (45), chrysoderol (46), luteolin (47), quercetin (48), dihydroapigenin (49) 3,4,3', 4'-tetrahydroxy- Delta -truxinate (50), (-) -isolariciresinol 3 alpha -O- beta -D-glucopyranoside (51), (+) -isolariciresinol 3 alpha / beta (52), (+), (+), (54), (55), (-), (-) Garesinol (56), (-) -medioresinol (57), (7S, 8R) -urolignoside (58), glochidioboside (59), (7R, 8S) -dihydrodehydrodiconiferyl alcohol 9-O- beta -D-glucopyranoside (60), (62), 1 Mine) -methyl nicotinate (63), cirsiumaldehyde (64), 5-hydroxymethylfurfural (65), p-Hydroxybenzoic acid (66), ethyl gallate (67), Syringate (68), p-coumaric acid (69), 71 (71), 72. Compound 1~31 is a new compound, compound 42 ~ 64 and 72 For the first time isolated from the genus cornel. The effect of compound 1~15 and 32~41 on the STAT3 pathway was evaluated based on luciferase reporter gene technique and its anti-inflammatory activity was evaluated. The experimental results showed that compound 3,12,33,35,36 showed obvious inhibitory activity to the STAT3 pathway and did not show cytotoxicity. The structure-activity relationship study showed that: a. When the compound's C-7 "is a beta conformation and condenses with glucose C-3'dehydration to form an ether bond, the STAT3 pathway shows obvious inhibitory activity. The C-7" of the B. compound shows an obvious inhibitory activity to the STAT3 pathway when it is formed by condensation of the C-6' dehydration of glucose to the STAT3 pathway, and C. and 7 alpha and beta Monod glucoside are shown to the STAT3 pathway. The inhibitory activity of the mouse peritoneal macrophage (RAW264.7) was induced by lipopolysaccharide (LPS). The inhibitory effect of the compound on the secretion of TNF- A and IL-6 was detected by ELISA reagent, and the anti-inflammatory activity of compound 32~41 was evaluated. The experimental results showed that the inhibitory effect of compound 33 on the secretion of inflammatory factor TNF- alpha was more than 50%, and the remainder was found. The inhibitory effects were not shown in the compound. In addition, the protective effects of PC12 cells 1~15 and 32~41 on the protection of hypoxia and glucose deficiency were also screened. The results showed that the cell survival rate of the compounds 1 and 3 of the selected 25 compounds increased, indicating that compounds 1 and 3 had certain protective effects on the PC12 cells damaged by OGD/R.
【學(xué)位授予單位】：北京中醫(yī)藥大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R284.1

【參考文獻】

相關(guān)期刊論文 前10條

1 閻新佳;溫靜;項崢;楊波;吳健;江培;崔琳琳;趙瑛;;連翹的化學(xué)成分研究[J];中草藥;2017年04期

2 胡佳;王澤宇;康敏;張兵;鄧峗;;江南紫金牛的化學(xué)成分研究[J];中草藥;2015年14期

3 白俊鵬;胡曉龍;蔣曉文;田星;趙慶春;;牛蒡根中咖啡酸類化學(xué)成分及其神經(jīng)保護活性研究[J];中草藥;2015年02期

4 紀(jì)明昌;肖世基;蔣舜媛;郭大樂;周燕;丁立生;;石柑子的化學(xué)成分研究[J];中草藥;2015年01期

5 于民豐;邵峗;陶燕鐸;;藏藥鮮卑花化學(xué)成分研究[J];中草藥;2014年24期

6 王威;劉小紅;高華;張英華;李相成;范美玲;董方言;;東北鐵線蓮地上部位化學(xué)成分研究[J];中草藥;2014年17期

7 任福才;王麗霞;王飛;李寶才;;綿棗兒化學(xué)成分研究[J];中草藥;2014年14期

8 齊敏友;謝高宇;陳凱;蘇燕慧;喻蘇青;劉浩然;;Total Triterpene Acids,Isolated from Corni Fructus,Ameliorate Progression of Renal Damage in Streptozotocin-Induced Diabetic Rats[J];Chinese Journal of Integrative Medicine;2014年06期

9 魏偉;范春林;王貴陽;唐海姣;王英;葉文才;;廣王不留行的化學(xué)成分研究[J];中草藥;2014年05期

10 郭潔;張曉雙;劉繼平;;山茱萸環(huán)烯醚萜總苷對晚期糖基化終末產(chǎn)物誘導(dǎo)的腎系膜炎癥反應(yīng)的調(diào)節(jié)[J];中成藥;2013年10期

，

本文編號：2086564