Anti-aging ‘Rasaayana’


“Jaraa-wyaadhi-winaashanam rasaayanam” (that which arrests aging and cures diseases) is the definition of the term “Rasaayana” in Ayurveda.

Aachaarya Charaka defined the term “Rasaayana” as…..

“Laabho-paayo hi shastaanam rasaadeenam rasaayanam” (Methods to achieve healthy, harmonic body-tissues is rasaayana)  

Charaka Samhita , Chikitsa Sthaana  1/1/7-8

The key properties of Guduchi (Tinospora cordifolia) described in Ayurveda are:
Wayhsthaapak and wyaadhiwinaashaka. This is why Guduchi (Tinospora cordifolia) is classified as one of “one of the Rasaayana drawyas”

All actions of Guduchi (Tinospora cordifolia) are in fact pharmacological actions of berberine. It is berberine that makes Guduchi (Tinospora cordifolia) a “Rasaayana” par excellence. Hence in this article I discuss the pharmacology of berberine.

I have described ethnopharmacology or phytopharmacology of Guduchi (Tinospora cordifolia) separately.

Pharmacology of Berberine



Molecular formula: C20H18NO4

Berberine is a quaternary ammonium salt. It belongs to protoberberine group of isoquinoline alkaloids. Berbirine is strongly yellow in color. Under ultraviolet light it shows a strong yellow fluorescence. It has pleiotropic properties and pharmacological actions.
Anti-inflammatory activity

Cyclooxygenase-2 (COX-2) plays a key role in the synthesis of prostaglandins which are elevated in inflammation. A study showed that treatment with berberine reduced prostaglandin production in oral cancer cell line. The effect was dependent on dose. Pretreatment with berberine of Wistar rats inhibited the production of PGE2 and inflammatory exudates in carrageenan-induced inflammation. This suggests that berberine exerts its anti-inflammatory action by inhibiting prostaglandin synthesis. 

Chi-Li Kuo, Chin-Wen Chhi, Tsung-Yun Liu, The anti-inflammatory potential of berberine in vitro and vivo, Cancer letters Volume 203, Issue 2, January 2004, Pages 127-137

Increased levels of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF–α) are markers of pulmonary inflammations. By suppressing the cytokine production berberine exhibits its anti-inflammatory activity in pulmonary inflammations.

Chang-Hsien Lee et al, Berberine suppresses inflammatory agents-induced interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF–α) productions via the inhibition of IκB degradation in human lung cells, Pharmacological Research, Volume 56, Issue 3, September 2007, Pages 193-201

Recently 13-alkyl-substituted berberines, [13-methylberberine (13-MB) and 13-ethylberberine (13-EB)] are shown to suppress the productions of IL-12, iNOS, TNF-α and COX-II better than what berberine does. Thus they are better anti-inflammatory agents than berberine.

Dong-Ung Lee et al, Effects of 13-alkyl-substituted berberine alkaloids on the expression of COX-II, TNF-α, iNOS, and IL-12 production in LPS-stimulated macrophages, Life Sciences, Volume 73, Issue 11, 1 August 2003, Pages 1401-1412
Antioxidant activity

Oxidative stress is the key factor in development of many diseases. Oxidative stress arises when the balance of intrinsic antioxidants and reactive oxygen species tilts towards the latter. By establishing this balance via various mechanisms berberine shows a potent antioxidant activity.
Yaw L. Siow et al, Redox regulation in health and disease-Therapeutic potential of berberine, Food Research International, Volume 44, Issue 8, October 2011, Pages 2409-2417

Immunomodulatory activity

Berberine showed a strong immunomodulatory effect. Immunomodulatory activity of Guduchi (Tinospora cordifolia) has been extensively investigated by using extract of the plant. Much of the work has also been conducted on berberine, jatrorhhizine, tinosporide and columbine. The possible mechanism of immunomodulatory activity was elucidated as activation of macrophages leading to increases in granulocytes.

Bhushan Patwardhan, Manish Gautam, Botanical immunodrugs: scope and opportunities, Drug Discovery Today, Volume 10, Issue 7, 1 April 2005, pages 495-502

Kostalova D et al, Antcompliment activity of Mahonia aquifolium bisbenzylisoquinoline alkaloids and berberine extract, Ceska a Slovenska Farmacie: Casopis Ceske Farmaceuticke Spolecnosti a Slovenske Farmaceuticke Spolecnosti 2001, 50(6): 286-289

Actions on the Skin

Exposure to Ultra Violet (UV) rays induces inflammation of the skin and expedites the aging process which is indicated by the elevation of matrix metalloproteinase-9 (MMP-9) and interleukin-6 (IL-6). Berberine suppresses MMP-9 and IL-6 expression. This effect is dependent on the dose of berberine used. This suggests that berberine may be used as an anti-skin aging product (‘Rasaayana’ concept of Ayurveda)

Sangmin Kim et al, Berberine inhibits TPA-induced MMP-9 and IL-6 expression in normal human keratinocytes, Phytomedicine Volume 15, Issue 5, 15 May, 2008, Pages 340-347

Sangmin Kim, Jin Ho Chung, Berberine prevents UV-induced MMP-1 and reduction of type-I procollagen expression in human dermal fibroblasts, Phytomedicine, Volume 15, Issue 9, 3 September, 2008, Pages 749-753.

Actions on the Endocrine System

Thymic stromal lymphopoietin (TSLP) plays a key role in allergic diseases such as atopic dermatitis and bronchial asthma. Berberine inhibits the production of TSLP in human mast cell line (HMC-1). Berberine inhibits production and mRNA expression of TSLP in HMC-1 cells. These findings suggest that berberine is useful in the treatment of inflammatory and atopic diseases.

Phil-Dong Moon, In-Hwa Choi, Hyung-Min Kim, Berberine inhibits the production of thymic stromal lymphopoietin by the blockade of caspase-1/NF-κB pathway in mast cells, International Immunopharmacology, Volume 11, Issue 11, November 2011, Pages 1954-1959.   

Antiviral activity

Berberine and the structurally related compounds show antiviral activity against human cytomegalovirus (anti-HCMV). This activity was found to be equal to that of ganciclovir. Berberine inhibits the replication of the virus after the latter has penetrated the host cell but before the viral DNA synthesis.

Kyoko Hayashi et al, Antiviral activity of berberine and related compounds against human cytomegalovirus, Bioorganic and Medicinal Chemistry Letters, Volume 17, Issue 6, 15 March 2007, Pages 1562-1564

Naturally occurring protoberberine alkaloids, berberine and berberrubine along with 9-substituded derivatives of berberine show anti-viral activity against human immune deficiency virus (HIV).  Berberine is more effective than the other two but is more toxic than the others. The anti-HIV activity of these compounds might be due to reverse transcriptase inhibitory activity and some other additional but ununderstood mechanism. 

Hardik S. Bodiwala, Synthesis of 9-substituted derivatives of berberine as anti-HIV agent, European Journal of Medicinal Chemistry, Volume 46, Issue 4, April 2011, Pages 1045-1049.

Recently berberine has been shown to exert antiviral activity against Influenza A virus

Cecil, Chad, Eric (Under the direction of Dr. Scott Laster), The Effects of Berbrrine on Influenza A virus, Influenza A virus-induced Inflammation and the Lipopolysaccharide-induced Synthesis of Prostaglandin E2 ,

Recently berberine at 150 µg/kg body weight has been shown to be effective against herpes simplex viruses 1 and 2 (HSV-1, HSV-2).

Mohmamed Dkhil, Saleh Al-Quraishy, Evaluation of antiviral activity of berberine against herpes simplex viruses, Journal of Pure and Applied Microbiology, 8:155-159. May 2014

Antifungal activity

Berberine, berberrubine and 13-substituted benzyl derivative of berberine show antifungal activities against human pathogenic fungi (Candida species). Synthesized compounds are more potent than berberine and berberrubine. Among the synthetic compounds 13-(4-isopropyl benzyl) berberine is most potent against Candida species.

KiDuk Park et al, Synthesis of 13-(substituted benzyl) berberine and berberrubine derivatives as antifungal agents, Bioorganic and Medicinal Chemistry Letters, Volume 16, issue 15, 1 August 2006, Pages 3913-3916

Anti-protozoal activity

In an in vitro study, semi-synthetic berberine analogue, 5,6-didehydro-8, 8-diethyl-13-oxodihydroberberine chloride showed activity against parasites of malaria, leishmaniasis and trypanosomiasis. While berberine hemisulfate is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds.

Mark Bahar et al, Potent antiprotozoal activity of a novel semi-synthetic berberine derivative, Bioorganic and Medicinal Chemistry Letters, Volume 21, Issue 9, 1 May 2011, Pages 2606-2610

Leishmaniasis is a vector-borne protozoal infection. It is caused by the Leishmania parasite. It is potentially lethal. It is endemic in 88 countries. Its annual incidence estimated as 1-1.5 million cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis.
The Leishmania parasite resides within macrophages. From this abode they deviously manipulate innate and acquired immune mechanism of the host. This ensures their survival within the hostile environment of macrophages and hinges on their capability to modulate macrophage effector function including production of reactive nitrogen intermediates
Naderer T, McConville MJ, (2008), The Leishmania-macrophage interaction: a metabolic perspective, Cell Microbiol 10: 301-308

Macrophages can induce host cells to produce cytokines that promote disease progression via regulation of T helper 1 (Th 1) and T helper 2 (Th 2) cells. The Th 1 cells enhance macrophage microbicidal activity, thus protecting the host from intracellular Leishmania pathogen. 

Roberts MT (2006), Current understandings on the immunology of leishmaniasis and recent developments in prevention and treatment. Br. Med Bull 75-76: 115-130

Conversely, for their survival, the parasites augment the Th 2 response leading to an increased secretion of IL-4 and IL-10, resulting in attenuation of host defense mechanism and Leishmania infection ensues.

Kane MM, Mosser DM, (2001), The role of IL-10 in promoting disease progression in leishmaniasis, J Immunol 166: 1141-1147.

Berberine chloride demonstrates potent anti-Leishmanial activity. It is suggested that besides being directly cytotoxic to Leishmania parasites, berberine chloride exerts immunomodulatory effect upon Leishmania infected macrophages. Moreover berberine has a high safety index which is necessary for anti-parasitic compounds.

Piu Saha et al, Berberine Chloride Mediates its Anti-Leishmanial Activity via Differential Regulation of the Mitogen Activated Protein Kinase Pathway in Macrophages, PLOS, Published: April 5, 2011, 

Action on Hematopoetic System

Berberine inhibits myeloma cells in the dose dependent manner. Its cytotoxic effect is explained by its direct blockade of potassium (K+) channels.

Sheng-Nan et al, Inhibitory effect of berberine on voltage and calcium-activated potassium currents in human myeloma cells, Life Sciences, Volume 62, Issue 25, 15 May 1998, pages 2283-2294

Actions on Musculoskeletal System

Berberine suppresses osteoclastic activity and bone resorption. The exact mechanism of this is unknown. However the recent evidence suggests that berberine inhibits osteoclast formation and their survival through suppression of NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), and Akt activation. Both pathways in the osteoclast lineage are highly sensitive to berberine treatment.
[Note: NF-κB is a protein complex that controls transcription of DNA, cytokine production and survival. Akt is a pathway that promotes survival and growth in response to extracellular signals]

Jin-Ping Hu et al, Berberine inhibits RANKL-induced osteoclast formation and survival through NF-κB and Akt pathways, European Journal of Pharmacology, Volume 580, Issues 1-2, 2 February 2008, pages 70-79

Actions on Nervous System

Administration of berberine protects and improves cell survival of the hippocampal cells in rat brain. This activity is also useful to prevent memory loss and improves memory deficit.

Lim JS et al, Neuroprotective effects of berberine in neurodegeneration model rats induced by ibotenic acid, Anim. Cells Syst. 2008; 12: 203-209

Berberine has neuroprotective effect on damaged neurons and neurodegenerating brains of neonatal animal model.

Lee T et al, Effect of berberine on cell survival in developing rat brain damaged by MK-801. Exp. Neurobiol. 2010; 19(3): 140-145

To evaluate anticonvulsant and antioxidant effect of berberine, temporal lobe epilepsy was induced in rats by intrahippocampal injection of kainite (dose: 4µg). Intraperitoneal administration of berberine at 25, 50 and 100mg/kg bodyweight was effective in controlling seizure. Further, pretreatment with berberine significantly decreased the Racine score and rate of incidence of seizure in rats. Berberine ameliorated the lipid peroxidation and nitrite level but had no effect on superoxide dismutase (SOD) activity. It seems that anticonvulsant activity of berberine is due lessening of oxidative stress.

Tourandokht Baluchnejad Mojarad, Mehrdad Roghani, The anticonvulsant and antioxidant effects of berberine in kainite-induced Temporal lobe epilepsy in rats, Basic Clin Neurosci. 2014, Spring; 5(2): 124-130    

Berberine inhibits the actions of morphine on the brain. This action is said to be via involvement of dopamine receptor. This suggests that berberine should be viewed as a potential antidote for attenuating morphine toxicity.

J. H. Yoo et al, Inhibitory effects of berberine against morphine-induced locomotor sensitization and analgesic tolerance in mice, Neuroscience, Volume 142, Issue 4, 3 November 2006, pages 953-961

In a study on mice, berberine attenuated the actions of nicotine, cocaine and morphine. Berberine is also demonstrated to modulate the activities of dopamine, nitric oxide and serotonin. Further berberine blocked the stimulant effects of ethanol. 

Pravinkumar Bhutada et al, Inhibitory effect of berberine on the motivational effects of ethanol in mice, progress in Neuro-Psychopharmacology and Biological Psychiatry, Volume 34, Issue 8, 1 December 2010, pages 1472-1479

In a study on mice, at doses of 5, 10 and 20 mg/kg bodyweight, berberine inhibited the enzyme monoamine oxidase-A (MAO-A), thus acting as an antidepressant. The effect was not dependent on dose. The dose 5 mg was as effective as 20mg. Administration of berberine to mice resulted in increased levels of norepinephrine (31%), serotonin (41%) and dopamine (31%) in the whole brain. At lower dose berberine did not affect the locomotor activity and barbiturate-induced sleep time. It produced mild hypothermic action in rats and analgesic effect in mice.

Shrinivas K. Kulkarni, Ashish Dhir, On the antidepressant-like action of berberine chloride, European Journal of Pharmacology, Volume 589, Issues 1-3, 28 July 2008, Pages 163-172 

Wen-Huang Peng et al, Berberine produces antidepressant-like effects in the forced swim test and in the tail suspension test in mice, Life Sciences Volume 81, Issue 11, 23 August 2007, Pages 933-938

SK Kulkarni and A Dhir are of the opinion that the antidepressant effect of berberine is due to the interaction of berberine with L-arginine-NO-cGMP pathway.

Kulkarni SK, Dhir A, Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in antidepressant activity of berberine chloride, Eur J Pharmacol. 2007 Aug 13; 569 (1-2): 77-83.

A series of novel synthetisized berberine derivatives are inhibitors of acetylcholinesterase and butyrylcholinesterase. Some of them also inhibit β-amyloid aggregation.

Ling Huang, Zonghua Luo et al, Synthesis and biological evaluation of a new series of berberine derivatives as dual inhibitors of acetylcholinesterase and butyrylcholinesterase, Bioorganic & Medicinal Chemistry, Volume 18, Issue 12, 15 June 2010, pages 4475-4484. 

Ling Huang et al, Berberine derivatives, with substituted amino groups linked at 9-position, as inhibitors of acetylcholinesterase/butyrylcholinesterase, Bioorganic & Medicinal Chemistry Letters, Volume 20, Issue 22, 15 November 2010, pages 6649-6652

Andig Shi et al, Synthesis, biological evaluation and molecular modeling of novel triazole containing berberine derivatives as acetylcholinesterase and β-amyloid aggregation inhibitors, Bioorganic and Medicinal Chemistry, Volume 19, Issue 7, 1 April 2011, Pages 2298-2305

As synthesized, hybride molecules of berberine inhibit acetylcholinesterase; they were used to treat Alzheimer’s disease. The hybrid molecules showed encouraging results and hence can be future candidates for the treatment of Alzheimer’s disease. The compounds showed capabilities (i) to inhibit multiple cholinesterases (ii) to prevent aggregation of β-amyloid and (iii) antioxidant activity. Berberine-pyrocatechol hybrid was much better inhibitor of acetylcholinesterase than unconjugated berberine and berberine-hydroquinone hybrid is the best antioxidant. 

Huailei Jiang et al, Benzenediol-berberine hybrids: Multifunctional agents for Alzheimer’s disease, Bioorganic & Medicinal Chemistry, Volume 19, Issue 23, 1 December 2011, Pages 7228-7235

Recently, a series of berberine-thiophenyl hybrids were designed and synthesized. They were found to be inhibitors of acetylcholinesterase, butyrylcholinesterase and β-amyloid and as antioxidants.  

Tao Su et al, Synthesis and biological evaluation of berberine-thiophenyl hybrids as multifunctional agents: Inhibiton of acetylcholinesterase, butyrylcholinesterase and Aβ aggregation and antioxidant activity, Bioorganic & Medicinal Chemistry, Volume 21, Issue 18, 15 September 2013, Pages 5830-5840

Berberine exerts neuroprotective effects in the cerebral ischemia-reperfusion injury in mice.

Bing Song et al, Berberine induces peripheral lymphocytes immune regulations to realize its neuroprotective effects in the cerebral ischemia/reperfusion mice, Cellular Immunology, Volume 276, Issues 1-2, March-April 2012, pages 91-100 

Yu-Shuang Chai et al, Effect of berberine on cell cycle arrest and cell survival during cerebral ischemia and reperfusion and correlationswith p53/cyclin D1 and PI3K/Akt, European Journal of Pharmacology, Volume 708, Issues 1-3, 15 May 2013, Pages 44-55 

Berberine protects the brain from ischemic brain injury. The results of the study showed that berberine inhibited generation of reactive oxygen species and subsequently release of pro-apoptotic factor cytochrome c and apoptosis-inducing factors. This protection is modulated via inhibition of mitochondrial apoptotic pathway.  

Xi-Qiao Zhou, Neuroprotective effects of berberine on stroke models in vitro and in vivo, Neuroscience Letters Volume 447, Issue 1, 5 December 2008, Pages 31-36

Recent studies show that by blocking potassium currents berberine protects the brain against ischemic damage.

Fang Wang et al, Effects of berberine on potassium currents in actually isolated CA 1 pyramidal neurons of rat hippocampus, Brain Research Volume 999, Issue 1, 27 February 2004, pages 91-97

Unlike the central nervous system, axons in the peripheral nervous system can regenerate following nerve injury. The effect of berberine was evaluated in rats with sciatic nerve injury.  The results showed that four weeks after administration of berberine at 20mg/kg body weight once a day for one week the thickness of remyelination of axon improved 1.4 fold. This showed that berberine promoted axonal regeneration in injured peripheral nerves. 

Ah Mi Han et al, Berberine promotes axonal regeneration in injured Nerves of the Peripheral Nervous System, J Med Food, 2012 Apr; 15 (4): 413-417
Actions on CVS

Type 2 diabetes was induced in rats by injecting streptozotocin at a dose of 35mg/kg body weight, and a high carbohydrate, high fat diet for 16 weeks. The rats were the administered low (75mg/kg), middle (150mg/kg) and high (300mg/kg) doses of berberine, 100 mg/kg fenofibrate, and 4mg/kg of rosiglitazone for another 16 weeks. The myocardial hypertrophy and interstitial fibrosis improved with middle and high doses of berberine. This shows that berberine may ameliorate myocardial damage in diabetics. 

Zhou Jiyin et al, Effect of berberine on Cdk9 and cyclin T1expressions in myocardium of diabetic rats, Journal of Medical College of PLA Volume 23, Issue 1, February 2008, Pages 45-51

By increasing 5’-activated protein kinase (AMPK) or 5’-adenosine monophosphate-activated protein kinase activity in insulin resistant H9c2 cells (a subclone of original cell line derived from rat heart tissue), berberine increases insulin sensitivity in the heart muscle. Berberine improves glucose uptake, glucose consumption and utilization in the myocardium. This action of berberine is beneficial for heart muscle in diabetics.
Wenguang Chang et al, Berberine improves insulin resistance in cardiomyocytes via activation of 5’- adenosine monophosphate-activated protein kinase, Metabolism, Volume 62, Issue 8, August 2013, Pages 1159-1167
For long it was hypothesized that some of the cardiovascular effects of berberine are mediated through activation of cardiac M2 muscarinic cholinergic receptors. The research by Satin Salehi and Theresa M Filtz has now proved that berberine is a muscarinic agonist at M2 receptors.
Satin Salehi, Theresa M Filtz, Berberine possesses muscarinic agonist-like properties in cultured rodent cardiomyocytes, Pharmacological Research, Volume 63, Issue 4, April 2011, pages 335-340
Seahyong Lee et al decided to verify the hypothesis: “Berberine could inhibit vascular smooth muscle cell (VSMC) proliferation as it did endothelial cells or cancer cells” Their results show that berberine significantly inhibits growth factor, mainly angiotensin II and heparin binding growth factor. This effect is achieved by delaying or partially suppressing activation of Akt pathway rather than ERK pathway. Further study shows that berberine is a potent agent to control restenosis after balloon angioplasty and warrants further study for its mechanism at a cellular level.
Seahyoung Lee et al, Berberine inhibits rat vascular smooth muscle proliferation and migration in vitro and improves neointima formation after balloon injury in vivo: Berberine improves neointima formation in a rat model; Atherosclerosis, Volume 186, Issue 1, May 2006, Pages 29-37

Kae-Woei Liang et al, Berberine suppresses MEK/ERK-dependent Egr-1 signalling pathway and inhibits vascular smooth muscle cell regrowth after in vitro mechanical injury, Biochemical pharmacology, Volume 71, Issue 6, 14 March 2006, Pages 806-817
After percutanoeus coronary artery angioplasty, platelet-derived growth factor (PDGF) is released from vascular smooth muscle cells (VSMCs), endothelial cells or macrophages. Berberine significantly inhibits PDGF-induced VSMC growth via activation of AMPK/p53/p21.
Kae-Woei Liang et al, Berberine inhibits platelet-derived growth factor-induced growth and migration partly through an AMPK-dependent pathway in vascular smooth muscle cells, European Journal of Pharmacology, Volume 590, Issues 1-3, 20 August 2008, Pages 343-354

Actions on RS

Bleomycin is notorious for causing lung injury and fibrosis. To investigate the effect of berbrerine treatment against these, 2.5 µg/kg body weight of bleomycin was instilled in the trachea of male Wistar rats. Administration of berberine significantly ameliorated the bleomycin mediated ill effects on the lung. Berberine reduced inflammatory cell infiltrate, blocked collagen accumulation, mast cell deposition and histamine release. Berberine enhanced the antioxidant status in the lungs. 

Palanivel Chitra, Gowrikumar Saiprasad, Ramar Manikandan, Ganapasam Sudhandiran, Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: A biphasic experimental study, Toxicology Letters, Volume 219, Issue 2, 23 May 2013, Pages 178-193.    
Actions on GI System
The side effects of antibiotic therapy for the treatment of Helicobacter pylori infection are unpleasant. Berberine was known to reduce Helicobacter pylori proliferation. Chiung-Hung Chang et al developed a novel nanoparticle berberine carrier with a heparin shell. The prepared nanoparticles significantly increased the suppressive effect of berberine on Helicobacter pylori growth while efficiently reducing cytotoxic effects in Helicobacter pylori-infected cells.
Chiung-Hung Chang et al, Development of novel nanoparticles shelled with heparin for berberine delivery to treat Helicobacter pylori, Acta Biomaterialia, Volume 7, Issue 2, February 2011, Pages 593-603
Berberine may improve colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation.
In-Ah Lee et al, Berberine ameliorates TNBS-induced colitis by inhibiting lipid peroxidation, enterbacterial growth and NF-κB activation, European Journal of pharmacology, Volume 648, Issues 1-3, 1 December 2010,pages 162-170
When administered intrarectally, TNBS (2,4,6-trinitrobenzenesulphonic acid) induces severe colonic inflammation. The colitis resulting from this procedure presents clinical and histopathological picture resembling that of Crohn’s disease.
Scheiffele F, Fuss IJ, Induction of TNBS colitis in mice, Curr Protoc Immunol. 2002 Aug; Chapter 15: Unit 15.19
In a study on mice researchers showed that berberine played an important regulatory role in modulating the balance of immune responses in TNBS-induced colitis. This study will also help us understand the regulatory mechanisms exerted by berberine in the treatment of inflammatory bowel disease (IBD).

Chengzhen Li et al, Berberine ameliorates TNBS induced colitis by inhibiting inflammatory responses and Th1/Th17 differentiation, Molecular Immunology, Volume 67, Issue 2, Part B, October 2015, Pages 444-454 

Tight junctions, also known as occluding junctions are the closely associated areas of two cells whose membranes join together forming a virtually impermeable barrier to fluid. It is a type of junctional complex present only in vertebrates. Maintenance of the mucosal barrier is a critical function of intestinal epithelial tight junction. Berberine can ameliorate pro-inflammatory cytokines induced intestinal epithelial tight junction damage. Berberine may be one of the targeted therapeutic agents that can restore barrier function in intestinal disease states.
Niang Li et al, Berberine attenuates pro-inflammatory cytokine-induced tight junction disruption in an in vitro model of intestinal epithelial cells. European Journal of Pharmaceutical sciences, Volume 40, Issue 1, 16 April 2010, Pages 1-8
Berberine exerts an anti-secretory action directly upon intestinal epithelial cells. The action is mediated by blocking potassium channels.
Cormac T Taylor et al, Berberine inhibits ion transport in human colonic epithelia, European Journal of Pharmacology, Volume 386, Issue 1, 26 February 1999, Pages 111-118

Actions on the Liver

A.  Hepatoprotection

Berberine protects the liver from carbon-tetra-chloride (CCl4)-induced liver injury. The hepatoprotection may be due to its free radical scavenging property, antioxidant property (attenuation of oxidative stress), as well as inhibition of inflammatory response in the liver.

Robert Domitrovic et al, Hepatoprotective activity of berberine is mediated by inhibition of TNF-α, COX-2 and iNOS expression in CCl4 –intoxicated mice, Toxocology, Volume 280, Issues 1-2, 4 February 2011, Pages 33-43   

Chronic carbon-tetra-chloride (CCl4) poisoning culminates into liver fibrosis. Berberine ameliorated liver fibrosis in mice with CCl4 –induced liver injury and inhibited the proliferation of hepatic stellate cell in dose- and time-dependent manner.

Jing Li et al, Hepatoprotective effects of berberine on liver fibrosis via activation of AMP-activated protein kinase, Life Sciences, Volume 98, Issue 1, 7 March 2014, Pages 24-30

B.  Viral Hepatitis

Berberine is a pharmacologically active constituent of Berberis vulgaris. Ethanolic extract of Berberis vulgaris containing berberine 100µg/ml inhibits replication of hepatitis C virus. This effect is attributed to lymphoproliferative effect and phagocytic and immunostimulant activity of berberine.

Doaa A Ghareeb et al, Biological assessment of Berberis vulgaris and its active constituent, berberine: Antibacterial, antifungal and anti-hepatitis C virus (HCV) effect, Journal of Medicinal Plants Research, Volume 7(21) pp 1529-1536, 3 June 2013;

C. Alcoholic Liver Disease
Consumption of alcohol produces a state of oxidative stress in liver. By reducing hepatic lipid peroxidation, elevating depleted levels of glutathione and repairing mitochondrial oxidative damage berberine reduces alcohol-induced liver fibrosis. Researchers feel that berberine can be a potential agent for preventing and treating alcoholic liver disease.
Pengcheng Zhang et al, Berberine protects liver from ethanol-induced oxidative stress and steatosis in mice, Food and Chemical Toxicology, Volume 74, December 2014, Pages 225-232
D. Non-alcoholic Fatty Liver Disease (NAFLD)
Non alcoholic liver disease (NAFLD) is the hepatic manifestation of obesity and metabolic syndrome. The precise mechanism of development of NAFLD being nebulous the mechanism by which berberine improves NAFLD is unclear. Defects in lipid metabolism-pathways, insulin resistance and inflammation are crucial players in the process of NAFLD. Recent evidence shows that berberine corrects all these and helps contain NAFLD.
Yang Liu et al, Update on Berberine in Nonalcoholic Fatty Liver Disease, Evidence-Based Complimentary and Alternative Medicine, Volume 2013, Article ID 308134, 8 pages;
Two week’s treatment with a berberine containing formula attenuated fatty degeneration of liver in obese Zucker diabetic rats.
H. L. Zhao et al, Sustained antidiabetic effects of a berberine-containing Chinese herbal medicine through regulation of hepatic gene expression, Diabetes, Volume 61, no. 4, pp. 933-943, 2012. 
J. Y. Zhou et al, Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic, hyperlipidemic rats, Biological and Pharmaceutical Bulletin, Volume 31, no. 6, pp. 1169-1176, 2008.
Treatment of hyperlipidemic hamsters with berberine significantly reduces fat storage in the liver.
J. M. Brusq et al, Inhibition of lipid synthesis through activation of AMP-kinase: an additional mechanism for hypolipidemic effects of berberine, Journal of Lipid Research, Volume 47, no. 6, pp. 1281-1288, 2000
Treatment for sixteen weeks with berberine could alleviate hepatic steatosis and decrease lipid content in the liver by 14% in rats with high-fat diet-induced fatty liver. Further berberine prevents the development of obesity, insulin resistance. Berberine may also prevent the development of liver fibrosis in alcoholic and non-alcoholic liver disease and steatosis due to hepatitis C infection. These activities are said to be due to antioxidant property of berberine.
X. Chang et al, Berberine reduces methylation of the MTTP promoter and alleviates fatty liver induced by high-fat diet in rats, Journal of Lipid Research, Volume 51, no. 9, pp. 2504-2515, 2010.
X. Zhang et al, Structural changes of gut micobacteria during berbrine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats, PLoS One Volume 7, no. 8, Article ID e42529, 2012.
B. J. Zhang et al, Protection by and anti-oxidant mechanism of berberine against rat liver fibrosis induced by multiple hepatotoxic factors, Clinical and Experimental Pharmacology and Physiology, Volume 35, no. 3, pp. 303-309, 2008
E. Hepatocarcinogenesis
Berberine arrests the cell cycle at G1/S phase. Berberine induces apoptotic events in hepatocellular carcinoma cells, through procaspase-9 and its effector caspases, procaspase-3 and procaspase-7.
Novia K et al, Berberine induces apoptosis via the mitochondrial pathway in liver cancer cells, Published online on: Wednesday, June 19, 2013.
Anti-diabetic activity

In a study, 36 adults with type 2 diabetes were treated with berberine for 3 months. The hypoglycemic effect of berberine was similar to that of metformin. Berberine also decreased total and low density cholesterol. 

Jun Yin et al, Efficacy of berberine in patients with type 2 diabetes mellitus, Metabolism, Volume 57, Issue 5, May 2008, Pages 712-717 

Both in vitro and in animal models, berberine increased insulin receptor (InsR) expression and improved glucose utilization. The study showed that berberine increased InsR messenger RNA and protein expression in a variety of human cell lines. Berberine reduced insulin resistance through protein kinase C-dependent insulin receptor expression. Thus berberine lowered blood sugar by a mechanism different from metformin and rosiglitazone. Further it can be said that berberine represents a different class of anti-hyperglycemic agents.   
Hao Zhang et al, Berberine lowers blood glucose in type 2 diabets mellitus patients through increasing insulin receptor expression, Metabolism, Volume 59, Issue 2, February 2010, pages 285-292

Wei-Jia Kong, Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression, Metabolism, Volume 58, Issue 1, January 2009, pages 109-119.

Chunhua Chen et al, Berberine inhibits PTP1B activity and mimics insulin action, Biochemical and Biophysical Research Communications, Volume 397, Issue 3, 2 July 2010, Pages 543-547.

Oxidative stress coexists with diabetes. By reducing oxidative stress berberine lowers raised blood sugar. After treatment with 150-300mg/kg bodyweight for 16 weeks, berberine showed protective effect for diabetes through increasing insulin expression, β cell regeneration, antioxidant enzyme activity and decreasing lipid peroxidation.

Jiyin Zhou et al, Protective effect of berberine on beta cells in streptozotocin-and high-carboyhdrate/high-fat-diet-induced diabetic rats, European Journal of Pharmacology, Volume 606, Issues 1-3, 15 March 2009, Pages 262-268 

Berberine is known as an AMP-activated protein kinase activator. Its insulin-independent hypoglycemic effect is related to inhibition of mitochondrial function, stimulation of glycolysis and activation of AMP-kinase pathway. Berberine may also act as an α-glucosidase inhibitor. In patients with poor β-cell function, berberine may improve insulin secretion by resuscitating exhausted islet cells. Its hypolipidemic activity protects cardiovascular system in diabetics. The antioxidant and aldose reductase inhibitory activities of berberine may alleviate diabetic nephropathy. Large scale trials are still necessary to evaluate the efficacy of berberine on diabetes and its related complications.  

Jun Yin et al, Effects and mechanisms of berberine in diabetes treatment, Acta Pharmaceutica Sinica B, Volume 2, Issue 4, August 2012, Pages 327-334

Li-Zhong Liu et al, Berberine modulates insuling signaling transduction in insulin-resistant cells, Molecular and Cellular Endocrinology, Volume 317, Issues 1-2, 12 April 2010, Pages 148-153
Glucagon-like peptide (GLP)-1 is a glucose-dependent insulinotrpoic hormone released from intestinal L cells. In an in vivo study on rats, 5-week treatment with berberine enhanced GLP-1 secretion induced by glucose load and promoted proglucagon mRNA expression as well as L cell proliferation in intestine.  
Yunli Yu et al, Modulation of glucagon-like peptide-1 release by berberine: In vivo and in vitro studies, Biochemical pharmacology Volume 79, Issue 7, 1 April 2010 Pages 1000-1006
By activating extracellular signal-regulated kinase, berberine increased glucose uptake in preadipocytes (Preadipocyte=undifferentiated fibroblast that can be stimulated to form an adipocyte) and adipocytes. Thus berberine increases glucose uptake through a mechanism distinct from insulin, and activated adenosine monophosphate-activated protein kinase seems to be involved in the metabolic effect of berberine.  
Libin Zhou et al, Berberine stimulates glucose transport through a mechanism distinct from insulin, Metabolism, Volume 56, Issue 3, March 2007, Pages 405-412

While natural alkaloid berberine is well accepted as an antidiabetic agent, some researchers found its use in clinical practice is limited because of its poor bioavailability. Their study shows that dihydroberberine has enhanced bioavailability and in vivo efficacy as an antidiabetic agent compared with berberine. 

Zhe Cheng et al, 8,8-Dimethyldihydroberberine with improved bioavaialability and oral efficacy on obese and diabetic mouse models, Bioorganic and Medicinal Chemistry, Volume 18, Issue16, 15 August 2010, pages 5915-5924

Treatment of streptozotocin-induced diabetic rats with berberine 200mg/kg body weight for 12 weeks, fasting blood glucose, urea nitrogen, creatinine and urine protein decreased. This was accompanied by a reduced aldose reductase activity and gene expression at both mRNA and protein levels. This suggests that berberine protects kidneys against diabetic nephropathy because of its antioxidative, antistress property.

Weihua Liu et al, Berberine inhibits aldose reductase and oxidative stress in rat mesangial cells cultured under high glucose, Archives of Biochemistry and Biophysics, Volume 475, Issue 2, 15 July 2008, pages 128-134

Berberine stimulates glucose uptake in rat-skeletal muscles in a dose and time dependent manner. The detailed study suggests that berberine stimulates glucose uptake through AMP-AMPK-p38MAPK pathway which may account for its hypoglycemic effects.

Zhe Cheng et al, Berberine-stimulated glucose uptake in L16 myotubes involves both AMPK and p38MAPK, Biochemica et Biophysica Acta (BBA) - General Subjects, Volume 1760, Issue 11, November 2006, Pages 1682-1689

Actions on Dyslipidemia

Berberine is a novel, natural lipid-lowering agent. Berberine at 100mg/kg/day enhances tumor necrosis factor-α (TNF- α) and thrombin induced endothelial tissue factor (TF) in human endothelial cells by 3.5-folds. Berberine should be considered for the treatment of dyslipidemia especially in statin resistant dyslipidemic subjects.

Eric W. Holy et al, Berberine a natural lipid-lowering drug, exerts prothrombotic effects on vascular cells, Journal of Molecular and Cellular Cardiology, Volume 46, Issue 2, February 2009, Pages 234-240 

Berberine lowers elevated serum levels of total cholesterol, triglycerides and LDL-cholesterol in hypercholesterolemic patients; and increases hepatic LDLR mRNA and protein levels through a post-transcriptional mechanism. By acting on multiple molecular targets as an inhibitor of PPARγ (peroxism proliferator activated receptorγ) and α berberine is a potential hypolipidemic, hypoglycemic and weight reducing agent.

Cheng Huang et al, Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARγ pathway, Biochemical and Biophysical Research Communication, Volume 348, Issue 2, 22 September 2006, Pages 571-578

Y. Hu, G. E. Davies, Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation, Phytomedicine, Volume 16, Issue 9, September 2009, Pages 864-873

Administration of 100mg/kg/day to rats improved insulin resistance, lowered elevated blood sugar, lowered elevated triglyceride and low density lipoprotein levels, increased high density lipoprotein levels, regulated lipid metabolism and nitric oxide levels. In conclusion, berberine restored endothelial dysfunction through enhanced nitric oxide bioavailability by up-regulating eNOS expression and down-regulating expression of NADPH oxidase.

Chunmei Wang et al, Ameliorative effect of berberine on endothelial dysfunction in diabetic rats induced by high-fat diet and streptozotocin, European Journal of Pharmacology, Volume 620, Issue 1-3, 12 October 2009, Pages 131-137

Li-Qin Tang et al, Effects of berberine on diabetes induced by alloxan and high-fat/high-cholesterol diet in rats, Journal of Ethnopharmacology, Volume 108, Issue 1, 3 November 2006, pages 109-115 

In another study on diabetic rats, intragastric administration of berberine (100 and 200mg/kg) significantly decreased fasting blood sugar levels, serum total cholesterol, triglyceride, LDL-cholesterol, effectively increased HDL-cholesterol and nitrous oxide  levels. Furthermore, berberine blocked the increase of malondialdehyde (MDA), increased super-oxide-dismutase (SOD) and glutathione peroxidase (GSH-px) contents in heart tissue. Furthermore as was evident by histopathological study, berberine restored damaged pancreatic tissue.

Li-Qin Tang et al, Effects of berberine on diabetes induced by alloxan and high-fat/high-cholesterol diet in rats, Journal of Ethnopharmacology, Volume 108, Issue 1, 3 November 2006, pages 109-115

Berberine improves free fatty acid-induced insulin resistance in myotubes through inhibiting fatty acid uptake at least in part by reducing PPARγ (peroxism proliferator activated receptor γ) and FAT/CD 36 expressions.

Yanfeng Chen et al, Berberine improves free-fatty-acid-induced insulin resistance in L6 myotubes through inhibiting peroxisome proliferator-activated receptor γ and fatty acid transferase expressions, Metabolism, Volume 58, Issue 12, December 2009, Pages 1694-1702

Berberine lowers elevated serum lipid levels in hyperlipidemic patients with chronic hepatitis or cirrhosis of the liver

Wei Zhao et al, Reduction of blood lipid by berberine in hyperlipidemic patients with chronic hepatitis or liver cirrhosis, Biomedicine & pharmacotherapy, Volume 62, Issue 10, December 2008, Pages 730-731

In elderly, statin-intolerant, hypercholesterolemic patients berberine lowered total cholesterol and low density lipoprotein levels

G. Marazzi et al, Long-term effects of nutraceuticals (berberine, red yeast rice, policosanal) in elderly hypercholesterolemic patients, Advances in therapy, Volume 28, no. 12, pp. 1105-1113, 2011  

In a study on hamsters berberine decreased LDL-cholesterol and reduced fat storage in the liver. By activation of AMP-kinase berberine inhibits lipid synthesis in human hepatocytes.

J. M. Brusq et al, Inhibition of lipid synthesis through activation of AMP kinase: an additional mechanism for the hypolipidemic effects of berberine, Journal of Lipid Research, Volume 47, no.6, pp. 1281-1288, 2006

Y. Ge et al, Berberine regulated Gck, G6pc, Pck1 and srebp-1c expression and activated AMP-activated protein kinase in primary rat hepatocytes, International Journal of Biological Sciences, Volume 7, No. 5, pp. 673-684, 2011

Actions on Urinary System

Diabetic nephropathy is heralded with renal fibrosis, glomerulosclerosis and tubulo-interstitial fibrosis. In vivo and in vitro studies showed that berberine ameliorates renal complications in diabetic mice.

These effects are due to antioxidant and anti-inflammatory activities of berberine.

Weihua Liu et al, Effects of berbeine on matrix accumulation and NF-kappa B signal pathway in alloxan-induced diabetic mice with renal injury, European Journal of pharmacology, Volume 638, Issues 1-3, 25July 2010, Pages 150-155

By inhibiting extracellular matrix (ECM) component and fibronectin (FN) expression berberine could improve renal function in rats and mice with diabetic nephopathy. The ameliorative effect might be associated with inhibition of NF-κB signaling pathway which is independent of hypoglycemic effect of berberine. 

Qin Jiang et al, Berberine attenuates lipopolysaccharide-induced extracellular matrix accumulation and infiltration in rat mesangial cells: Involvement of NF-κB signaling pathway, Molecular and Cellular Endocrinology, Volume 331, Issue 1, 1 January 2011, Pages 34-40
The possible mechanism by which berberine exerts renoprotective effects may be related to inhibition of glycosylation and improvement of antioxidant status that in turn upregulates the expressions of renal nephrin and podocin, the protein component of filtration unit of kidney.

Duo Wu et al, Ameliorative effect of berberine on renal damage in rats with diabetes induced by high fat-diet and streptozotocin, Phytomedicine, Volume 19, Issues 8-9, 15 June 2012, Pages 712-718

Recently Sphingosine kinase-Sphingosine 1-phosphate (Sph K-S1P) signaling pathway has been implicated by some researchers in the pathogenesis of diabetic nephropathy (DN). Mice with diabetic nephropathy were treated with oral berberine 300mg/kg body weight/day for 12 weeks. Berberine lowered elevated blood glucose, blood urea nitrogen, serum creatinine, albuminuria and kidney/body weight ratio. Berberine also prevented renal hypertrophy, transforming growth β1 (TGF-β 1) polypeptide synthesis, accumulation of fibronectin (FN) and collagen IV found in the basal lamina. Moreover berberine down-regulated the elevated levels of mRNA and protein SphK1 and S1P production as well. These findings suggest that the inhibitory effect of berberine on the activation of SphK1-S1P signaling pathway in kidney of diabetic mouse is a novel mechanism by which berberine exerts protective effects on kidneys in diabetic nephropathy.

Tian Lan et al, Berberine ameliorates renal injury in diabetic C57BL/6 mice: Involvement of suppression of SphK-S1P signaling pathway, Archives of Biochemistry and Biophysics, Volume 502, Issue 2, 15 October 2010, Pages 112-120

Berberine has antioxidant effect. In Wistar rats at 5-20mg/kg body weight berberine increased urine output accompanied by increased pH and sodium-potassium excretion and decreased calcium excretion. This effect was similar to that of hydrochlorothiazide. Berberine at 10mg/kg body weight prevented deposition of calcium oxalate crystals in renal tubules (anti-urolithic property)

Samra Bashir, Anwar H. Gilani, Anti-urolithic effect of berberine is mediated through multiple pathways, European Journal of Pharmacology, Volume 651, Issues 1-3, 25 January 2011, Pages 168-175 
Anticancer activity

Berberine inhibits neuroblastoma through inhibition of fundamental characteristics of cancer stemness. (Stemness= an essential characteristic of a stem cell that distinguishes it from ordinary cells)

C. R. Naveen, Sagar Gaikwad, Reena Agrawal-Rajput, Berberine induces neuronal differentiation through inhibition of cancer stemness and epithelial-mesenchymal transition in neuroblastoma cells, Phytomedicine, Volume 23, Issue 7, 15 June 2016, Pages 736-744

Growth inhibitory effect of berberine was well documented. Berberine inhibits invasion, induces cell cycle arrest and apoptosis in human cancer cells. The anti-inflammatory property of berberine involving inhibition of Signal Transducer and Activator of Transcription 3 (STAT3) activation has also been documented. By inhibiting STAT3 berberine inhibits the growth of nasopharyngeal carcinoma (NPC) cells. In future berberine may be used for treating nasopharyngeal carcinoma.   

Chi Man Tsang et al, Berberine suppresses tumorigenecity and growth of nasopharyngeal carcinoma cells by inhibiting STAT3 activation induced by tumor associated fibroblasts, BMC Cancer 2013, 13: 619 

By intercalating (Intercalate= Reversible inclusion) into DNA berberine inhibits cancer of thymus gland.

Saran A et al, 1H NMR investigation of the interaction of berberine and sanguinarine with DNA, Indian Journal of Biochemistry & Biophysics, 1995, 32(2): 74-77

Berberine exhibits the ability to induce apoptosis in promyelocytic leukemia HL-60 cells. At the concentration of 25µg/ml, berberine showed that only about 20% cells underwent early time (6hours) apoptosis. However at extended time (up to 48 hours) number of cells underwent apoptosis in S phase. 

Chi L. Kuo et al, Berberine complexes with DNA in the berberine-induced apoptosis in humal leukemic HL-60 cells, Cancer Letters, Volume 93, Issue 2, 13 July 1995, Pages 193-200  

Silvia Letasiova et al, Berberine-antiproliferative activity in vitro and induction of apoptosis/necrosis of U937 and B16 cells.

Sona Jantova et al, Berberine induces apoptosis through a mitochondrial/caspase pathway in human promonocytic U937 cells, Toxicology in Vitro, Volume 21, Issue 1, February 2007, Pages 25-31

Berberine exerts a dose and time-dependent inhibitory effect on motility and invasion ability of highly metastatic A549 cells. Berberine exerts its effect via regulating tissue inhibitor of metalloproteinase-2 (TIMP-2) and urokinase-plasminogen activator inhibitor (PAI). It is said that the inhibitory effect is likely to be at the transcriptional level. These findings suggest that berberine possesses an anti-metastatic effect in non-small cell lung cancer cell and may be helpful for its treatment.  

Pei-Ling Peng et al, Inhibitory effect of berberine on the invasion of human lung cancer cells via decreased productions of urokinase-plasminogen activator and matrix metalloproteinase-2, Toxicology and Applied Pharmacology, Volume 214, Issue 1, 1July 2006, Pages 8-15

Yung-Tsuan Ho et al reported that berberine inhibited the migration and invasion of human squmaous cell carcinoma-4 tongue cancer cells. The action was mediated via multiple pathways.

Yung-Tsuan Ho et al, Berberine suppresses in vitro migration and invasion of humal SSC-4 tongue carcinoma cells through the inhibitions of FAK, IKK, NF-κB, u-PA and MMP-2 and-9, Cancer Letters, Volume 279, Issue 2, 8 July 2009, Pages 155-162

Berberine inhibits esophageal cancer in a dose dependent manner. The study also reveals that berberine may be useful as one of alternative therapies for esophageal cancers.

Izuka N, Inhibitory effect of Coptidis rhizome and berberine on proliferation of human esophageal cancer cell lines, Cancer Letters, 2000 Jan 1; 148(1): 19-25

Berberine inhibits the proliferation and reproduction of tumerigenic microorganisms, viruses such as Helicobacter pylori and hepatitis B virus. It also shows transcriptional regulation of some oncogene and carcinogenesis-related gene expression and interaction with both DNA and RNA. Besides berberine is a broad spectrum enzyme inhibitor, which affects N-acetyltransferase, cyclooxygenase-2 and topoisomerase activities and gene/protein expression. Thus by multiple mechanisms berberine inhibits tumor growth and metastasis. Recent research shows that berberine exerts anticancer activity both in vitro and in vivo through different mechanisms.

Sun Y et al, A systematic review of the anticancer properties of berberine, a natural product from Chinese herbs, Anticancer drugs, 2009 Oct; 20(9):757- 69

By inducing apotosis, cell cycle arrest, berberine inhibits Hepatoma HepG2 cells. Furthermore berberine enhanced DNA methylation level in whole genome. These findings suggest that antiproliferation effect of berberine might be mediated by the unique epigenetic modifying mechanism.  

Zhang L, et al, Antiproliferation of berberine is mediated by epigenetic modification of constitutive androstane receptor (CAR) metabolicpathway in hepatoma cells, Sci Rep. 2016 Jun 17; 6: 28116

Zhaojian Liu et al demonstrated that berberine inhibited human osteosarcoma cells. The inhibition was attributed to cell cycle arrest at G1 and G2/M and apoptosis of the osteosarcoma cells by inflicting DNA damage.

Zhaojian Liu et al, Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Volume 662, Issues 1-2, 9 March 2009, Pages 75-83

Berberine induces cell growth arrest, apoptosis in human colorectal cancer cells. This anti-cancer action is mediated via multiple pathways.

Rojsanga Piyanuch et al, Berberine, a natural isoquinoline alkaloid, induces NAG-1 and ATF3 expression in human colorectal cancer cells, Cancer Letters, Volume 258, Issue 2, 18 December 2007, Pages 230-240

The treatment of human prostate cancer cells with berberine induced dose-dependent apoptosis. Berberine did not harm normal, non-neoplastic human prostate epithelial cells. Berberine-induced apoptosis was associated with the disruption of the mitochondrial membrane potential, release of apoptogenic molecules. This effect of berberine on prostate cancer was regulated by reactive oxygen species. Berberine may be a promising therapeutic candidate for prostate cancer.

Syed M. Meeran et al, Berberine-induced apoptosis in human prostate cancer cells is inhibited by reactive oxygen species generation, Toxicology and Applied Pharmacology, Volume 229, Issue 1, 15 May 2008, Pages 33-43

Interactions and Toxicity

Berberine interacts with metformin and limits its tissue uptake.
Berbrrine may interact with macrolide antibiotics leading to cardiotoxicity.
Too much berberine taken at once can result in stomach upset, abdominal cramping and diarrhea.

The standard dose is 900-2000 mg a day divided into three or four doses.
Berberine should be taken with a meal or soon after to take advantage of its hypoglycemic and hypolipidemic activity 

Samra Bashir, Anwar H. Gilani, Anti-urolithic effect of berberine is mediated through multiple pathways, European Journal of Pharmacology, Volume 651, Issues 1-3, 25 January 2011, Pages 168-175 


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