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Monday 1 September 2014

Berberine

Berberin.svg




Berberine

C20H18NO4

336.00

mp......203-204


Berberine is a quaternary ammonium salt from the protoberberine group of isoquinoline alkaloids. It is found in such plants asBerberis [e.g. Berberis aquifolium (Oregon grape), Berberis vulgaris (barberry), Berberis aristata (tree turmeric)], Hydrastis canadensis (goldenseal), Xanthorhiza simplicissima (yellowroot), Phellodendron amurense[2] (Amur cork tree), Coptis chinensis(Chinese goldthread 黄连素 or Huang Lian Su), Tinospora cordifoliaArgemone mexicana (prickly poppy), and Eschscholzia californica (Californian poppy). Berberine is usually found in the roots, rhizomes, stems, and bark.[citation needed]
Due to Berberine's strong yellow color, Berberis species were used to dye wool, leather and wood. Wool is still today dyed with berberine in northern India. Under ultraviolet light, berberine shows a strong yellow fluorescence,[3] so it is used in histology forstaining heparin in mast cells.[4] As a natural dye, berberine has a colour index of 75160.

1H NMR




(400 MHz, CD3OD) δ: 9.75 (1H, s, H-8), 8.69 (1H, s, H-13), 8.10 (1H, d, J = 8.3 Hz, H-11),
7.98 (1H, d, J = 8.4 Hz, H-12), 7.64 (1H, s, H-1), 6.94 (1H, s, H-4),
 6.09 (2H, s, OCH2O), 4.91 (2H, t, J = 6.4, H-6), 4.18 (3H, s, 9-OCH3),
 4.09 (3H, s, 10-OCH3), 3.24 (2H, t, J = 6.4 Hz, H-5)








盐酸小檗碱









13 C NMR


(100 MHz, CD3OD) δ: 151.0 (C-10), 150.8 (C-3), 148.7 (C-2), 
144.6 (C-9), 145.2 (C-8), 138.5 (C-13a), 134.0 (C-12a), 
130.7 (C-4a), 126.8 (C-11), 123.3 (C-12), 122.1 (C-8a), 
120.7 (C-13b), 120.3 (C-13), 108.2 (C-4), 105.3 (C-1), 
102.5 (OCH2O), 61.3 (C-9, OCH3), 56.4 (C-10, OCH3), 56.0 (C-6), 27.0 (C-5)

[1H,13C] 2D NMR Spectrum
Image

MASS
http://scialert.net/fulltext/?doi=rjmp.2008.1.9



H. Raja Naika and V. Krishna, 2008. Micropropagation, Isolation and Characterization of Berberine from Leaves of Naravelia zeylanica(L.) DC.. Research Journal of Medicinal Plant, 2: 1-9.

DOI: 10.3923/rjmp.2008.1.9 

URL: http://scialert.net/abstract/?doi=rjmp.2008.1.9


The Soxhlet extraction of 100 g of dried leaves yielded 12 g of crude methanolic extract. Ten gram of the crude extract yielded 270.0 mg of total alkaloids from the leaves extract. The presence of the alkaloid confirmed qualitatively by Dragendorff’s, Mayer’s and Wagner’s tests. (Kokate et al., 1990) The separation of berberine was done by preparative TLC method and the yield was 70 mg from in vivo leaf extract. The constituent was characterized by subjecting it to IR, 1H NMR and MASS spectral studies.
Spectral Characterization of Code RA 
IR (Kbr):2820 cm-2 (C-H str)
1597 cm-2 (C = C, C = N str)
1354-1383 cm-2 (C-H deformation)
1060 cm-2 (C-O str) (Fig. 2)

1H NMR (CDCL3):δ 1.75 (m, 2H,-CH2-)
δ 2.4 (m, 2H, N+-CH3)
δ 3.9 (s, 6H, 2 X OCH3)
δ 6.0 (s, 2H, O-CH2-O)
δ 6.6-9.4 (m, 6H, Ar-H) (Fig. 3)


Fig. 2:IR spectrum of berberine

Fig. 3:1H NMR spectrum of berberine

Mass spectra (EI-MS):Molecular formula:C20H19NO4
Molecular weight:336.37
EIMS: (m/z):336 (m+, 20%), 322 (35%), 281 (50%), 267 (38%), 207 (76%), 147 (100%) (Fig. 4)






Biosynthesis of berberine


Berberine
Berberin.svg
Identifiers
CAS number2086-83-1 
PubChem2353
ChemSpider2263 Yes
UNII0I8Y3P32UF Yes
DrugBankDB04115
ChEBICHEBI:16118 Yes
ChEMBLCHEMBL12089 
Jmol-3D imagesImage 1
Properties
Molecular formulaC20H18NO4+
Molar mass336.36122 g/mol
Appearanceyellow solid
Melting point145°C[1]
Solubility in waterslowly soluble[1]
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)


Berberine

Title: Berberine
CAS Registry Number: 2086-83-1
CAS Name: 5,6-Dihydro-9,10-dimethoxybenzo[g]-1,3-benzodioxolo[5,6-a]quinolizinium
Additional Names: 7,8,13,13a-tetradehydro-9,10-dimethoxy-2,3-(methylenedioxy)berbinium; umbellatine
Molecular Formula: [C20H18NO4]+
Literature References: Tautomeric alkaloid widely distributed in nine or more botanical familes but occurs most frequently inBerberidaceae. A component of many traditional medicines, first isolated in 1826. Structure: Perkin, Robinson, J. Chem. Soc. 97,305 (1910). Biosynthesis: J. R. Gear, I. D. Spenser, Can. J. Chem. 41, 783 (1963). Pharmacology: Fukuda et al., Chem. Pharm. Bull. 18, 1299 (1970). Total synthesis: Kametani et al., J. Chem. Soc. C 1969, 2036. NMR: G. Blasko et al., Heterocycles 27, 911 (1988). HPLC determn in biological fluids: C.-M. Chen, H.-C. Chang, J. Chromatogr. B 665, 117 (1995). Clinical evaluation in malaria: W. D. Sheng et al., East Afr. Med. J. 74, 283 (1997). Review of biological activities: F. E. Hahn, J. Ciak, in Antibioticsvol. 3, D. Gottlieb et al., Eds. (Springer-Verlag, New York, 1975) pp 577-584; of chemistry, distribution and use: R. S. Thakur, S. K. Srivastava, Curr. Res. Med. Aromat. Plants 4, 249-272 (1982). Review of antidiarrheal action: A. W. Baird et al., Adv. Drug Delivery Rev. 23, 111-120 (1997).
Properties: Yellow needles from ether, mp 145°: Gadamer, Arch. Pharm. 243, 33 (1905). uv max: 265, 343 nm. pK 2.47.
Melting point: mp 145°: Gadamer, Arch. Pharm. 243, 33 (1905)
pKa: pK 2.47
Absorption maximum: uv max: 265, 343 nm
Derivative Type: Acid sulfate
Additional Names: Berberine bisulfate
Molecular Formula: C20H19NO



.....................
Berberine is isoquinoline alkaloid. Molecular formula: [C20H18NO4]+, molecular weight: 336.37 and its chemical structure is as follows:
Figure imgb0002



  1. The Merck Index, 10th Ed. (1983), p.165, Rahway: Merck & Co.
  2. Jump up^ Zhang, Q; Cai, L; Zhong, G; Luo, W (2010). "Simultaneous determination of jatrorrhizine, palmatine, berberine, and obacunone in Phellodendri Amurensis Cortex by RP-HPLC". Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 35 (16): 2061–4. doi:10.4268/cjcmm20101603.PMID 21046728.
  3. Jump up^ Weiß, Dieter (2008). "Fluoreszenzfarbstoffe in der Natur" (in German). Retrieved 17 July 2009.


EXTRA'S YOU WOULD LIKE

Berberine, also called umbellatine, is an isoquinoline alkaloid represented by the following formula, which is a major active component in such plants as Coptidis chinensis Franch., Berberis amurensis Rupr., Berberis sargentiana Schneid andNandina domestica etc. Clinically, berberine is mainly used to treat diarrhea caused by bacteria with the most important advantage of having little side effects. Berberine has been used as a broad spectrum antibiotic for many years, and is effective on inhibition and elimination of various Gram-positive and Gram-negative bacteria, fungi, moulds, viruses, protozoa and nematode.
Figure US20100113494A1-20100506-C00002

Structure of Berberine
Since 1950s, a large number of animal experiments and clinical trials have been carried out by some specialists, researchers and clinicians with berberine hydrochloride which is widely used in clinic, and the results showed that berberine are effective on the therapy of diabetes mellitus and their complications besides being antibiotic. Some research literatures are summarized in the following Table I:

TABLE I
Summary of animal experiments and clinical trials on treating diabetes mellitus with berberine
AuthorsResults of animal studies and clinical trialsLiterature
Qiming CHEN,Berberine possesses advantages of both sulfonylureas andActa
Mingzhi XIEbiguanides. It can lower blood glucose levels of both normal micePharmaceutica
(Institute ofand alloxan-induced diabetic mice, and antagonize the increase ofSinica, 1986,
Materia Medica,blood glucose levels induced by exogenous glucose or21(6): 401-406.
Chinese Academyepinephrine. It has powerful effect on lowering blood glucose
of Medicallevels and long action time lasting up to 5-6 hours. Berberine can
Sciences)also improve abnormal blood coagulation and prevent
atherosclerosis. It had a significant effect on lowering blood
glucose at a dose of 40 mg/kg.
Yanxie NI, et. al.60 cases of type 2 diabetic patients were treated with berberineJournal of
(The 208th hospitaland the treatment was lasted for 1-3 months. The results showedIntegrated
of PLA)that the fasting blood glucose decreased averagely by 5.1 mmol/LTraditional and
and the efficiency was 90%. It was found by pathologicWestern
examinations that berberine could promote the regeneration andMedicine, 1988,
functional recovery of pancreatic beta-cells. No abnormality was8(12): 711-713.
observed for all patients in the hepatic and renal functions and
hemogram during the treatment and no obvious adverse effect
was found.
Guoying LIU30 cases of type 2 diabetic patients were treated with berberineNew use of old
(Pengze traditionaland the efficiency was 90%. Berberine was significantly effectivedrug, 1992, 1: 3-4.
Chinese medicalfor the patients with light or moderate diabetes mellitus. In
hospital, Jiujiang,addition, it also showed effects on lowering blood pressure and
Jiangxi)blood fat, and preventing infection and the occurrence of
complication etc.
Mianrong YU, et.75 cases of type 2 diabetic patients were treated with berberineBeijing Medical
al. (Builderand the efficiency was 69.33%. Three diabetic symptoms, i.e.Journal, 1994,
hospital of Beijing)polyuria, polydipsia and polyphagia, disappeared for all patients16(2): 117.
within two weeks after administration of berberine accompanying
the decrease of blood glucose. The diabetic patients have been
treated with berberine and observed for 4 years, and none of them
was observed with adverse effects or hypoglycemia regardless of
dose. In addition, 11 patients had normal blood glucose with
reduced dose more than 3 years.
Faguang HU, et. al.60 cases of type 2 diabetic patients were treated with berberineThe Practical
(The Shanxuanand the efficiency was 90%. Berberine had a mild and lastingJournal of
people's hospital,effect on lowering blood glucose, making the blood glucose startIntegrating of
Henan)to lower after about 2 weeks, and achieving its maximum curativeChinese with
effect within 8 weeks. For all patients, berberine made theModern Medicine,
diabetic symptoms disappearing or being relieved and showed1995, 8(6):
good effects on common diabetic complications. In addition, 4358-359.
patients with overweight recovered their normal weights. No
toxic and/or adverse effects were observed.
Jiaqing ZHANGBerberine has a certain effect on increasing insulin sensitivity andLiaoning Journal
(Changhai hospital,can improve insulin resistance with an insulin action index (IAI)of Practical
the 2nd militarysimilar to metformin.Diabetology,
surgeon college)1999, 1(4): 56-57.
Changshan LIU, etRenal failure often occurs to most of diabetic patients with theChinese Journal of
al. (Weifangdeterioration of conditions. Berberine, a traditional Chinese drug,Diabetes, 1996,
medical college,has a significant effect on reversing diabetic renal failure and4(3): 163-166.
Shandong)inhibiting the activities of the polyol and kidney aldose reductases
of diabetic mice to lower urine protein.
Jinhua TONG49 cases of type 2 diabetic patients were treated with berberineNew Journal of
(Sanitation Schooland the efficiency was 63.3%. Berberine can suppressTraditional
of Fengtai, Anhui)glyconeogenesis and glycogenolysis, slow down insulinChinese Medicine,
metabolism and promote the sensitivity of peripheral tissue cells1997, 29(3):
to insulin by lowering the activity of the sympathetic nerve and33-34.
inhibiting the adrenal cortical function. It can also promote the
regeneration and functional recovery of pancreatic cells.
Huading YU,The effect of berberine on treating non-insulin dependent diabeticMedical Journal of
Laiwen YANpatients was evaluated. The patients were divided randomly into 2Communications,
(Shanghai seamangroups, and each group had 30 persons. One group took berberine1995, 9(4): 45.
hospital)and another took Diamicron. After 4 weeks treatment, the
variations of the concentrations of blood glucose and blood serum
insulin were compared between the two groups, and the results
showed that the two groups had similar curative effects and no
severe adverse effects were observed.
Yunfei ZHANGFor 20 cases of type 2 diabetic patients, their conditions were notChinese Journal of
(Hangzhouimproved significantly after they took oral anti-diabetic drugs forIntegrated
sanatorium of Airlowering blood glucose such as D860 and glibenclamide etc.Traditional and
Force)Then, they were treated with berberine. The fasting blood glucoseWestern
levels of all patients were lowered to normal levels 3 monthsMedicine, 1999,
later. The effect of berberine on lowering blood glucose was19(9): 567.
dependent on dose, and no side effects such as hypoglycemia
were observed.
Hong ZHU, Wei112 cases of type 2 diabetic patients were treated with berberineJournal of Jining
DAI (Affiliatedand the efficiency was 90%, which showed that berberine had aMedical College,
hospital of Jininggood effect on lowering blood glucose. Specifically, berberine1999, 22(3): 67.
medical college)had mild and lasting effect of lowering blood glucose without
severe toxicity, side effects and damages to liver and renal
function, and had good curative effect on common complications
of diabetes mellitus.
Litian SHI, et al.68 cases of type 2 diabetic patients were treated with berberine.Shanxi Clinical
(TaiyuanThe blood glucose levels of the patients were loweredMedicine, 2000,
commercial staffsignificantly, and the total efficiency was 86.8%. The action9(3): 181-182.
hospital)mechanism of berberine on lowering blood sugar was multiple.
The blood serum insulin levels of the patients increased
significantly after the treatment.
Dongkou WANG57 cases of type 2 diabetic patients were treated with a secondZhejiang Journal
(Taizhou Healthgeneration sulfonylureas drug alone or in combination withof Integrated
center, Jiangsu)metformin. However, secondary failure occurred 3 years later.Traditional
Thus, berberine was taken additionally. The blood glucose levelsChinese and
of the patients were lowered more or less 1 month later, and totalWestern
efficiency was 81%.Medicine, 2002,
12(1): 50.
Jiandong JIANG etBerberine can interact with insulin receptors and increaseCN01121906.8
al.significantly the expressions of insulin receptor genes and
peroxisome proliferator activated receptor genes. Therefore,
berberine can be used as an insulin sensitizer to treat type 2
diabetes mellitus alone or in combination with insulin or other
type 2 diabetic drugs.
Kaimin WUHighly soluble berberines such as berberine sulfate and berberineWO03090749A1,
phosphate etc. are easily dissolved in water, which may improveCN1771944A
the absorption of the drugs in organism and thus enhance
significantly their curative effect. Thus, they can be used to treat
and prevent diabetes mellitus or its complications.
Recently, berberine has been widely used to treat type 2 diabetes mellitus in clinic. It was found in an initial research that the antihyperglycemic activity of berberine was in association with its activities of resisting hyperglycemic hormones and promoting the regeneration and functional recovery of pancreatic beta-cells (Hongyan ZHENG, Weiren XU, Chinese herbal medicine. 2004, 35: 708-711). Such research showed that 5-100 μmol of berberine could increase the glucose consumption in HepG2 cells by 32-60%, but it did not stimulate βTC3 cells to secrete insulin. So it was concluded that the antihyperglycemic activity of berberine acted by increasing the glucose consumption of liver cells instead of stimulating to secrete insulin, i.e., the antihyperglycemic activity of berberine acted through liver cells without depending on insulin.
Juan WANG (Juan WANG, China and foreign medical Journal. 2004, 2(12): 65-66) reported that it was observed clinically that the blood glucose levels decreased and the blood serum insulin levels increased when berberine was used to treat diabetes mellitus, which indicated that berberine could promote the regeneration and functional recovery of pancreatic beta-cells besides its resistance to the hyperglycemic hormones. Berberine can also inhibit gluconeogenesis and improve glycolysis, thereby lowering the blood glucose. Thus, the antihyperglycemic activity of berberine belongs to the field of insulin sensitizer. Berberine also has positive effects on preventing diabetes mellitus complications because of its activities of anti-hypertension, anti-hyperlipidemia and anti-infection.



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