CN108484542B - Methylene butyrolactone diterpenoid compound with hypoglycemic activity and preparation method and application thereof - Google Patents
Methylene butyrolactone diterpenoid compound with hypoglycemic activity and preparation method and application thereof Download PDFInfo
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- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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Abstract
The invention discloses an methylene butyrolactone diterpenoid compound with hypoglycemic activity. The molecular formula of the compound is C20H28O5The structure end has an alpha, beta-unsaturated lactone ring, and the molecular chain contains carboxyl substituent. The research on the activity of reducing blood sugar in vitro shows that the methylene butyrolactone diterpenoid compound provided by the invention has strong inhibitory activity on alpha-amylase, alpha-glucosidase and the like, and IC50Only about one-fifteenth of the positive drug (acarbose). The methylene butyrolactone diterpenoid compound with hypoglycemic activity provided by the invention has strong in-vitro hypoglycemic activity, and is expected to be developed into a new hypoglycemic medicament.
Description
Technical Field
The invention relates to a compound with hypoglycemic activity, in particular to a new methylene butyrolactone diterpenoid compound with hypoglycemic activity extracted and separated from traditional Chinese medicine lizardtail and application thereof in preventing and treating diabetes, belonging to the technical field of medicines.
Background
With the increasing living standard of people, the prevalence rate of diabetes is increased sharply, and currently, the number of diabetic patients is more than 3.6 hundred million worldwide, and 6 hundred million is predicted to be broken through by 2030. The number of diabetes patients in China is about 9200 ten thousand, and the diabetes patients become the most countries in the world. If metabolic disorder in the body of a diabetic patient cannot be controlled in time, various acute and chronic complications of the whole body can be caused, and multiple organ tissue damages can be affected, such as multiple complications and even death caused by blindness, cardiovascular and cerebrovascular diseases, renal failure, limb gangrene and the like. Diabetes has become the third leading "health killer" for human death following cardiovascular disease, malignancy.
At present, medicines for effectively treating diabetes are lacked, western medicines are mainly used for controlling symptoms, and the medicines have serious adverse reactions such as gastrointestinal tract reaction, liver injury, hypoglycemia and the like. Diabetes is called diabetes in traditional Chinese medicine. Two thousand years ago, "diabetes mellitus" was recorded in Su Wen (plain questions) and Ling Shu (Ling Shu) of Huang Di Nei Jing, the history of the traditional Chinese medicine for treating diabetes mellitus is long, rich experience is accumulated, and the traditional Chinese medicine has the characteristics of mild and lasting effect, small toxic and side effect, suitability for long-term administration of diabetics and the like, has the comprehensive advantage that chemical medicines can not replace in the aspects of effectively preventing and relieving the diabetes mellitus and the complications thereof and improving the insulin sensitivity, and has attracted more and more attention in the medical field. Therefore, the novel natural product with anti-diabetic activity is searched from the traditional Chinese medicine with obvious hypoglycemic activity, and has wide development prospect.
Saururus chinensis is dry aerial parts of Baill of Saururus chinensis (Lour.) of Saururaceae, has effects of inducing diuresis to reduce edema, clearing heat and detoxicating, is mainly used for treating urinary tract infection, urinary calculus, nephritic edema, leukorrhagia, etc., and is also used as a folk common medicine in Korea, Japan, etc. The Chinese lizardtail herb is proved to have obvious hypoglycemic activity and can improve insulin resistance and blood coagulation abnormality through various pharmacodynamic experiments of integral animals, cells, molecules and the like at home and abroad, but the research reports on the chemical components with hypoglycemic bioactivity in the Chinese lizardtail herb are few.
Disclosure of Invention
The purpose of the invention is as follows: the invention aims to overcome the defects of the prior art, and systematically and deeply researches the chemical components and the blood sugar reducing activity of the saururus chinensis and separates and obtains the methylene butyrolactone diterpenoid compound with the blood sugar reducing activity.
The technical scheme is as follows: in order to achieve the above purpose, the invention adopts the technical scheme that:
the structure formula of the methylene butyrolactone diterpenoid compound with the hypoglycemic activity is as follows:
molecular formula C20H28O5The structure end has an alpha, beta-unsaturated lactone ring, the molecular chain containsThe invention is named as saururus chinensis diterpene D by a carboxyl substituent.
The extraction and separation method of the methylenebutyrolactone diterpene with the hypoglycemic activity provided by the invention comprises the following steps:
(1) extracting aerial parts of dried Saururi herba with solvent or supercritical CO2Extracting with extraction method, recovering solvent to obtain Saururi herba extract;
(2) separating Saururi herba extract by silica gel column chromatography, MCI column chromatography and preparative liquid chromatography to obtain desired compound Saururi herba diterpene D.
In the above preparation method, the extraction method in step 1 may be cold soaking, percolating, microwave extracting, ultrasonic extracting, reflux extracting, or supercritical CO extraction2Extraction, etc.
Performing silica gel column chromatography (wet column loading, dry sample loading), performing gradient elution by adopting petroleum ether-ethyl acetate (volume ratio of 50: 1-0: 100) and ethyl acetate-methanol (volume ratio of 50: 1-0: 100) to obtain 10 components (Fr.1-Fr.10), performing MCI column pigment removal (90% ethanol elution) on Fr.4 part according to thin-layer chromatography detection, performing ODS medium-pressure preparation, performing gradient elution by using methanol-water (1: 1-0: 1) to obtain Fr.4-1-Fr.4-5, and performing semi-preparative HPLC separation on Fr.4-3, wherein the chromatographic conditions are as follows: inertsil ODS-3(20 mm. times.250 mm, 10 μm) column, methanol-water (7: 3) as mobile phase, flow rate of 10ml/min, and room temperature, collecting TRAnd (3) obtaining the methylene butyrolactone diterpenoid compound by a chromatographic peak of 13.8-14.5 min.
The methylene methyl butyrolactone diterpenoid compound with hypoglycemic activity provided by the invention is prepared from saururus chinensis diterpenoid D and pharmaceutically acceptable carriers into tablets, capsules, injections, powder injections, granules, fat emulsions, microcapsules, dropping pills, ointments, transdermal controlled release patches and other dosage forms.
When the methylene butyrolactone diterpenoid compound provided by the invention is prepared into tablets, the methylene butyrolactone diterpenoid compound and lactose or corn starch are added with a lubricant magnesium stearate if necessary, and the mixture is uniformly mixed, granulated and then tableted to prepare the tablets.
When the methylene butyrolactone diterpenoid compound provided by the invention is prepared into capsules, the methylene butyrolactone diterpenoid compound and carrier lactose or corn starch are uniformly mixed, granulated and then encapsulated to prepare the capsules.
When the methylene butyrolactone diterpene compound provided by the invention is prepared into granules, the methylene butyrolactone diterpene compound and a diluent lactose or corn starch are uniformly mixed, granulated, dried and prepared into granules.
The methylene butyrolactone diterpene compound provided by the invention is prepared by adding a carrier according to a conventional pharmaceutical method when being prepared into powder injection and injection.
The methylene butyrolactone diterpenoid compound provided by the invention is prepared by adding a carrier according to a conventional pharmaceutical method when being prepared into dosage forms such as a fat emulsion, an ointment or a transdermal controlled release patch.
The invention provides an application of a methylene butyrolactone diterpenoid compound (saururus chinensis diterpenoid D) with hypoglycemic activity in preparation of a medicament for preventing and treating diabetes.
As a preferable scheme, the application of the methylenebutyrolactone diterpenoid compound with hypoglycemic activity provided by the invention in preparing a medicament for treating diabetes has obvious inhibition effect on two important targets of alpha-glucosidase and PTPIB for preventing and treating type 2 diabetes, particularly has the inhibition effect on the alpha-glucosidase which is more than 10 times higher than that of clinical hypoglycemic drug acarbose, and has obvious biological activity.
Has the advantages that: compared with the prior art, the methylene butyrolactone diterpenoid compound with hypoglycemic activity provided by the invention has the following advantages:
the invention carries out systematic and intensive research on the chemical components of saururus chinensis and shows that a methylene butyrolactone diterpenoid compound (saururus chinensis diterpenoid D) separated from saururus chinensis is a new compound through the analysis of spectrum and mass spectrum data. And in-vitro hypoglycemic activity research shows that the methylene butyrolactone diterpenoid compound (saururus chinensis diterpenoid D) provided by the invention has strong inhibitory activity on alpha-amylase, alpha-glucosidase and the like, and IC50Only about one-fifteenth of the positive drug (acarbose). The invention provides the hypoglycemic teaThe invented product is an excellent new compound for reducing blood sugar, and can be developed into new medicine for reducing blood sugar.
Drawings
FIG. 1 is a schematic view of the structure of a methylenebutyrolactone diterpene compound;
FIG.2 shows the preparation of a diterpene compound from methylenebutyrolactone1A HNMR map;
FIG. 3 shows the preparation of a diterpene compound from methylenebutyrolactone13C NMR chart;
Detailed Description
The invention will be better understood from the following examples. However, those skilled in the art will readily appreciate that the specific material ratios, process conditions and results thereof described in the examples are illustrative only and should not be taken as limiting the invention as detailed in the claims.
EXAMPLE 1 preparation of Diterpene Compounds of Alomethylbutyrolactone
(1) Taking 8kg of saururus chinensis coarse powder, and adopting supercritical CO2Extracting under 30MPa at 50 deg.C for 2 hr with 95% ethanol as entrainer in an amount 1 times of the medicinal materials, and concentrating under reduced pressure to obtain extract (about 110 g);
(2) subjecting the extract obtained in the step (1) to silica gel column chromatography (wet column loading and dry sample loading), performing gradient elution by adopting petroleum ether-ethyl acetate (volume ratio of 50: 1-0: 100) and ethyl acetate-methanol (volume ratio of 50: 1-0: 100) to obtain 10 components (Fr.1-Fr.10), performing detection by thin-layer chromatography, subjecting Fr.4 to MCI column pigment removal (90% ethanol elution), performing ODS medium-pressure preparation, performing gradient elution by using methanol-water (1: 1-0: 1) to obtain Fr.4-1-Fr.4-5, and subjecting Fr.4-3 to semi-preparative HPLC separation, wherein the chromatographic conditions are as follows: inertsil ODS-3(20 mm. times.250 mm, 10 μm) column, methanol-water (7: 3) as mobile phase, flow rate of 10ml/min, and room temperature, collecting TRAnd (3) obtaining the methylene butyrolactone diterpenoid compound by a chromatographic peak of 13.8-14.5 min. (yield: 15.0mg) and the structural formula is shown in FIG. 1.
Structural analysis of the methylenebutyrolactone diterpene compound:
light yellow gum (MeOH), HR-ESI-MSm/z:347.1859[M-H]-，(calcd for C20H27O5347.1864), are combined1H-NMR、13C-NMR to confirm the molecular formula to be C20H28O5。1H NMR(400MHz,CDCl3) 4 methyl protons 1.67(3H, s, H-16),1.59(3H, s, H-17),1.26(3H, s, H-19),2.17(3H, d, J ═ 1.2Hz, H-20), 4 olefinic protons 6.87(1H, t, J ═ 7.4Hz, H-10),5.96(1H, d, J ═ 1.2Hz, H-2),5.48(1H, t, J ═ 7.9Hz, H-5),5.13(1H, t, J ═ 7.2Hz, H-14), and 5 methine signals 2.59(2H, d, J ═ 8.0Hz, H-6),2.32(4H, m, H-12,13),2.10(2H, m, H-9), 1.63H-8 (m, H-8);13c NMR showed a total of 20C signals including two carbonyl signals, delta 172.80(C-2),169.46(-COOH),8 olefinic carbon signals 154.61(C-3),152.24(C-4),144.64(C-10),132.43(C-15),131.68(C-11),123.50(C-14),116.51(C-2),108.10(C-5), and one heteroatom-attached carbon signal 72.82 (C-7).
1H-1In the HCOSY spectrum, 5.13(1H, t, J ═ 7.2Hz, H-14) is associated with 1.67(3H, s, H-16),1.59(3H, s, H-17), respectively, indicating that the structure contains an isobutenyl fragment, 6.87(1H, t, J ═ 7.4Hz, H-10) is associated with 2.10(2H, m, H-9), 2.10(2H, m, H-9) is associated with 1.63(2H, m, H-8), 2.32(2H, m, H-12,13) is associated with 5.13(1H, t, J ═ 7.2Hz, H-14) (fig. 2-1-3). Combining the above spectral data, and comparing with literature, the compound is determined to be methylene butyrolactone diterpene, the double bond of C-10 and C-11 is determined to be in trans configuration according to the chemical shift of H-10 located at a lower field, consistent with saururus chinensis diterpene B and C, and shifted to a lower field by 0.93ppm with saururus chinensis diterpene A in cis form, the double peak of 5.46(1H, d, J-9.3 Hz, H-5) is changed into triple peak 5.48(1H, t, J-7.9 Hz, H-5), and simultaneously 4.62(1H, d, J-9.3 Hz, H-6) is shifted to a high field by 2.59(2H, d, J-8.0 Hz, H-6), and the carbon spectrum is also shifted to a high field by 71.75(C-6) to 40.86(C-6), indicating that no hydroxyl substitution is at the 6 position. The absolute configuration of C-7 is to be further determined, and the compound is searched to be a novel compound which is not documented and is named as saururus chinensis diterpene D.
Example 2 in vitro hypoglycemic assay
1. Alpha-amylase inhibitory Activity
70 μ L of PBS salt buffer (pH 6.9) was sequentially added to a 96-well plate sieve,30 mu g/mL alpha-amylase 5 mu L, adding a certain concentration of methylenebutyrolactone diterpene sample 2 mu L, after 10min of warm bath at 37 ℃, adding 20 mu L of 10% starch substrate, reacting for 20min at 37 ℃, adding 3 mu L I2-stopping the reaction with KI solution and determining the absorbance value (A value) at 550 nm; blank control (buffer only), negative control (buffer and enzyme only) and positive control (acarbose) were set simultaneously. All the above samples and blank reactions were repeated 3 times, and the average was taken as experimental data.
Inhibition ratio (%) [ (A)Enzyme-AEnzyme space)-(ASample (A)-ASample space)]/(AEnzyme-AEnzyme space)×100％
The experimental results are as follows: the inhibition rates of 6 concentrations of compound methylenebutyrolactone diterpene, 1 ug/mL, 2 ug/mL, 5 ug/mL, 10 ug/mL, 20 ug/mL and 50 ug/mL, on alpha-amylase were 2.17%, 5.42%, 12.83%, 23.25%, 39.48% and 63.09%, respectively. Computing IC5029.71. mu.g/ml. (acarbose IC50492.18. mu.g/ml).
2. Alpha-glucosidase inhibitory activity
Sequentially adding 76 mu LPBS buffer solution (pH is 6.8) and 2 mu L alpha-glucosidase (1U/mL) into a 96-well plate sieve, adding 2 mu L of a certain concentration of methylenebutyrolactone diterpene sample solution, incubating at the constant temperature of 37 ℃ for 10min, adding a substrate PNPG20 mu L, reacting at the constant temperature of 37 ℃ for 30min, and measuring the absorbance value (A value) at the wavelength of 405 nm; blank control (buffer only), negative control (buffer and enzyme only) and positive control (acarbose) were set simultaneously. All the above samples and blank reactions were repeated 3 times, and the average was taken as experimental data.
Inhibition ratio (%) [ (A)Enzyme-AEnzyme space)-(ASample (A)-ASample space)]/(AEnzyme-AEnzyme space)×100％
The experimental results are as follows: the inhibition rates of 6 concentrations of compound methylenebutyrolactone diterpene, namely 1 mu g/mL, 2 mu g/mL, 5 mu g/mL, 10 mu g/mL, 20 mu g/mL and 50 mu g/mL, on alpha-glucosidase are respectively 1.07%, 3.56%, 10.48%, 26.76%, 49.80% and 78.13%. Computing IC5020.47. mu.g/ml, acarbose IC50318.20 mug/ml。
EXAMPLE 3 preparation of capsules
Taking the methylene butyrolactone diterpene prepared in the example 1 and adding a proper amount of starch serving as an auxiliary material, fully and uniformly mixing, and then encapsulating to prepare capsules for oral administration.
EXAMPLE 4 preparation of tablets
Taking the methylene butyrolactone diterpene prepared in the example 1, adding lactose and corn starch, adding a proper amount of lubricant magnesium stearate, uniformly mixing, granulating, and tabletting to prepare tablets.
The above embodiments are merely illustrative of the technical concept and features of the present invention, and the present invention is not limited thereto, and equivalent changes and modifications made according to the spirit of the present invention should be covered thereby.
Claims (4)
1. The methylene butyrolactone diterpenoid compound with the hypoglycemic activity is characterized in that the structural formula is as follows:
2. the process for producing a hypoglycemic active dimethylbutyrolactone diterpene compound according to claim 1, which comprises the steps of:
(1) taking 8kg of saururus chinensis coarse powder, and adopting supercritical CO2Extracting under 30MPa at 50 deg.C for 2h with 95% ethanol as entrainer in an amount 1 times of the medicinal materials, and concentrating under reduced pressure to obtain extract;
(2) performing silica gel column chromatography on the extract obtained in the step (1), performing gradient elution by adopting petroleum ether-ethyl acetate and ethyl acetate-methanol in the volume ratio of 50: 1-0: 100 to obtain 10 components Fr.1-Fr.10, and performing detection by adopting thin layer chromatography, namely passing the Fr.4 part through an MCI column and adopting 90% ethanolAfter pigment is removed by elution, preparing by ODS medium pressure, performing gradient elution by methanol-water with the volume ratio of 1: 1-0: 1 to obtain Fr.4-1-Fr.4-5, separating Fr.4-3 by semi-preparative HPLC, wherein the chromatographic conditions are as follows: inertsil ODS-3, specification 20mm × 250mm, 10 μm chromatographic column, mobile phase of methanol-water with volume ratio of 7: 3, flow rate of 10ml/min, column temperature of room temperature, collecting TRAnd (3) obtaining the methylene butyrolactone diterpenoid compound by a chromatographic peak of 13.8-14.5 min.
3. Use of the methylenebutyrolactone diterpene compound having hypoglycemic activity according to claim 1 for the preparation of a medicament for treating diabetes.
4. The use of the methylenebutyrolactone diterpene compound having hypoglycemic activity according to claim 3 for the preparation of a medicament for treating diabetes, wherein the diabetes is type I or type II diabetes.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101225042A (en) * | 2008-02-18 | 2008-07-23 | 珍奥集团股份有限公司 | Yacon diterpene acid compounds, medicine composition, preparation method and use in preparation of medicine treating diabetes mellitus |
| CN101786953A (en) * | 2010-03-17 | 2010-07-28 | 北华大学 | Kaurane-type diterpenoid compound as well as preparation method and medical application thereof |
| CN101899028A (en) * | 2010-08-05 | 2010-12-01 | 肖培根 | New furanditerpenoid compound, preparation method and application thereof |
| CN102731277A (en) * | 2011-04-12 | 2012-10-17 | 中国科学院上海药物研究所 | Diterpene compound Lobophytumin A, Lobophytumin B, Lobophytumin C, Lobophytumin D, Lobophytumin E and Lobophytumin F, and preparation method and application thereof to preparation of medicament |
| CN104327023A (en) * | 2014-10-31 | 2015-02-04 | 中国药科大学 | 7-ketone carbonyl dihydrobenzofuran neolignan as well as preparation method and application of 7-ketone carbonyl dihydrobenzofuran neolignan |
| CN104557658A (en) * | 2014-11-03 | 2015-04-29 | 南昌大学 | Haematinic acid esterified chain diterpenoid compound as well as preparation and application thereof |
| CN107840814A (en) * | 2016-09-21 | 2018-03-27 | 复旦大学 | Monocyclic diterpene compound cassipourol and preparation method thereof and the purposes in pharmacy |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080206365A1 (en) * | 2007-02-28 | 2008-08-28 | Yoshihisa Tachibana | Diterpene compounds having an atisane framework, compositions thereof, and methods of production |
-
2018
- 2018-05-16 CN CN201810470466.6A patent/CN108484542B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101225042A (en) * | 2008-02-18 | 2008-07-23 | 珍奥集团股份有限公司 | Yacon diterpene acid compounds, medicine composition, preparation method and use in preparation of medicine treating diabetes mellitus |
| CN101786953A (en) * | 2010-03-17 | 2010-07-28 | 北华大学 | Kaurane-type diterpenoid compound as well as preparation method and medical application thereof |
| CN101899028A (en) * | 2010-08-05 | 2010-12-01 | 肖培根 | New furanditerpenoid compound, preparation method and application thereof |
| CN102731277A (en) * | 2011-04-12 | 2012-10-17 | 中国科学院上海药物研究所 | Diterpene compound Lobophytumin A, Lobophytumin B, Lobophytumin C, Lobophytumin D, Lobophytumin E and Lobophytumin F, and preparation method and application thereof to preparation of medicament |
| CN104327023A (en) * | 2014-10-31 | 2015-02-04 | 中国药科大学 | 7-ketone carbonyl dihydrobenzofuran neolignan as well as preparation method and application of 7-ketone carbonyl dihydrobenzofuran neolignan |
| CN104557658A (en) * | 2014-11-03 | 2015-04-29 | 南昌大学 | Haematinic acid esterified chain diterpenoid compound as well as preparation and application thereof |
| CN107840814A (en) * | 2016-09-21 | 2018-03-27 | 复旦大学 | Monocyclic diterpene compound cassipourol and preparation method thereof and the purposes in pharmacy |
Non-Patent Citations (2)
| Title |
|---|
| Bioactive constituents from the green alga Caulerpa racemosa;Peng Yang,et al.;《Bioorganic & Medicinal Chemistry》;20141127;第23卷;第38-45页 * |
| Sauruchinenols A and B, unprecedentedmonocyclic diterpeneswith new carbon skeleton from the aerial parts of Saururus chinensis;Xiu Gao，et al.;《Fitoterapia》;20161129;第116卷;第116-120页 * |
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