Okayama University


Okayama University Medical Research Updates (OU-MRU) Vol.75

January 20, 2020

Source: Okayama University (JAPAN), Public Relations Division
For immediate release: 22 January 2020
Okayama University research: More than just daily supplements — herbal medicines can treat stomach disorders

(Okayama, 22 January) In a recent study published in Scientific Reports, researchers at Okayama University illustrate the potential of berberine, a herbal Chinese medicine, in reducing inflammation within the digestive tract.

Inflammatory bowel disease (IBD) is a commonly occurring, painful condition which leads to severe swelling within the stomach and intestine. The goal of IBD treatment is to keep this swelling in check. However, not all patients respond effectively to drugs available for this purpose. Dr.TAKAHARA Masahiro’s research team at Okayama University has now shown that berberine, a supplement routinely used for diarrhea and diabetes in China, is also effective in reducing IBD-related swelling.

IBD occurs when specialized cells known as CD4+ T cells found in the digestive system do not function properly. This results in inflammation, or the swelling, bloating and pain associated with IBD. Berberine is extracted from shrubs such as tree turmeric and is known to have anti-inflammatory properties. Furthermore, it activates AMPK, a protein responsible for controlling the growth and survival of all eukaryotic cells including CD4+ T cells. Based on these characteristics of berberine the team sought out to examine whether the supplement might be helpful in IBD.

CD4+ T cells were isolated from lamia propria of colitic mice with severe intestinal inflammation and were subsequently treated with berberine. For inflammation to ensue CD4+ T cells first have to release chemicals known as cytokines. The cytokine levels in the isolated CD4+ T cells were therefore substantially high. However, these cytokine levels dropped soon after berberine treatment. To investigate what specifically drove the cytokine plummet, the researchers artificially manipulated AMPK within the cells and found that changes in AMPK activity directly altered cytokine levels. This confirmed the notion that berberine reduced the inflammation caused by CD4+ T-cells by virtue of its AMPK-modulating activity. These effects of berberine were then tested in same colitic mice as above. As observed in the cells, not only was cytokine release greatly reduced in the gut of these mice, but AMPK activity was also high.

The gut harbors various species of bacteria within it, the composition of which directly impacts gastrointestinal health. Therefore, the gut microbes of these mice were also carefully examined. Berberine treatment seemed to reduce the species of certain bacteria, making the composition more homogenous. However, whether this modification of bacterial makeup plays a role in the protective mechanism of berberine is yet to be determined.

“In summary, we showed for the first time that [berberine] ameliorated CD4+ T cell-related chronic colitis in a mouse model with changes in gut microbiota via AMPK activity”, concludes the research team. Targeting AMPK in these cells opens a new avenue for IBD treatment which needs to be explored further.

T cells and inflammation: T cells are protective cells that prevent infections by warding off microbes. A subgroup of T cells, known as helper T cells detect potentially dangerous stimuli and release chemicals known as cytokines. CD4+ T cells are an example of such T cells. The release of cytokines sets in motion a chain of events leading to swelling, redness, heat, and pain (collectively called inflammation) thereby creating a detrimental environment for microbes. The helper T cells of certain individuals do not function properly and release cytokines even in a situation that does not normally react excessively. This leads to disorders such as IBD, wherein certain internal organs are always inflamed.

AMPK: AMPK or 5' adenosine monophosphate-activated protein kinase is a protein that regulates energy production within the cell. AMPK indirectly controls the cellular fate by driving growth, cell division, metabolism and response to stress. By virtue of its role, AMPK is now a popular therapeutic target and drugs that modulate AMPK activity are being investigated for chronic inflammation, obesity, diabetes and hyperlipidemia.

Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Takuya Adachi, Yasuyuki Shimomura, Hiroshi Matsushita, Tien Thi Thuy Nguyen, Kazuko Koike, Airi Ikeda, Shiho Takashima, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kinugasa, Yusaku Sugihara, Keita Harada, Shingo Eikawa, Hidetoshi Morita, Heiichiro Udono & Hiroyuki Okada. Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. Scientific Reports, (2019) 9:11934.
DOI : https://doi.org/10.1038/s41598-019-48331-w

Correspondence to
Clinical Fellow TAKAHARA Masahiro, M.D., Ph.D.
Department of Gastroenterology and Hepatology,
Graduate School of Medicine, Dentistry and Pharmaceutical
Sciences, Okayama University, 2-5-1 Shikata-cho, Kita-ku,
Okayama 700-8558, Japan
E-mail: mtakahara(a)okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Further information
Okayama University
1-1-1 Tsushima-naka , Kita-ku , Okayama 700-8530, Japan
Public Relations Division
E-mail: www-adm(a)adm.okayama-u.ac.jp
For inquiries, please contact us by replacing (a) with the @ mark.

Website: //www.okayama-u.ac.jp/index_e.html
Okayama Univ. e-Bulletin: //www.okayama-u.ac.jp/user/kouhou/ebulletin/
We love OKAYAMA UNIVERSITY: https://www.youtube.com/watch?v=7cXlttQIk3E
Okayama University Image Movie(2018)

Okayama University Medical Research Updates (OU-MRU)
The whole volume : OU-MRU (1- )
Vol.1:Innovative non-invasive ‘liquid biopsy’ method to capture circulating tumor cells from blood samples for genetic testing
Vol.2:Ensuring a cool recovery from cardiac arrest
Vol.3:Organ regeneration research leaps forward
Vol.4:Cardiac mechanosensitive integrator
Vol.5:Cell injections get to the heart of congenital defects
Vol.6:Fourth key molecule identified in bone development
Vol.7:Anticancer virus solution provides an alternative to surgery
Vol.8:Light-responsive dye stimulates sight in genetically blind patients
Vol.9:Diabetes drug helps towards immunity against cancer
Vol.10:Enzyme-inhibitors treat drug-resistant epilepsy
Vol.11:Compound-protein combination shows promise for arthritis treatment
Vol.12:Molecular features of the circadian clock system in fruit flies
Vol.13:Peptide directs artificial tissue growth
Vol.14:Simplified boron compound may treat brain tumours
Vol.15:Metamaterial absorbers for infrared inspection technologies
Vol.16:Epigenetics research traces how crickets restore lost limbs
Vol.17:Cell research shows pathway for suppressing hepatitis B virus
Vol.18:Therapeutic protein targets liver disease
Vol.19:Study links signalling protein to osteoarthritis
Vol.20:Lack of enzyme promotes fatty liver disease in thin patients
Vol.21:Combined gene transduction and light therapy targets gastric cancer
Vol.22:Medical supportive device for hemodialysis catheter puncture
Vol.23:Development of low cost oral inactivated vaccines for dysentery
Vol.24:Sticky molecules to tackle obesity and diabetes
Vol.25:Self-administered aroma foot massage may reduce symptoms of anxiety
Vol.26:Protein for preventing heart failure
Vol.27:Keeping cells in shape to fight sepsis
Vol.28:Viral-based therapy for bone cancer
Vol.29:Photoreactive compound allows protein synthesis control with light
Vol.30:Cancer stem cells’ role in tumor growth revealed
Vol.31:Prevention of RNA virus replication
Vol.32:Enzyme target for slowing bladder cancer invasion
Vol.33:Attacking tumors from the inside
Vol.34:Novel mouse model for studying pancreatic cancer
Vol.35:Potential cause of Lafora disease revealed
Vol.36:Overloading of protein localization triggers cellular defects
Vol.37:Protein dosage compensation mechanism unravelled
Vol.38:Bioengineered tooth restoration in a large mammal
Vol.39:Successful test of retinal prosthesis implanted in rats
Vol.40:Antibodies prolong seizure latency in epileptic mice
Vol.41:Inorganic biomaterials for soft-tissue adhesion
Vol.42:Potential drug for treating chronic pain with few side effects
Vol.43:Potential origin of cancer-associated cells revealed
Vol.44:Protection from plant extracts
Vol.45:Link between biological-clock disturbance and brain dysfunction uncovered
Vol.46:New method for suppressing lung cancer oncogene
Vol.47:Candidate genes for eye misalignment identified
Vol.48:Nanotechnology-based approach to cancer virotherapy
Vol.49:Cell membrane as material for bone formation
Vol.50:Iron removal as a potential cancer therapy
Vol.51:Potential of 3D nanoenvironments for experimental cancer
Vol.52:A protein found on the surface of cells plays an integral role in tumor growth and sustenance
Vol.53:Successful implantation and testing of retinal prosthesis in monkey eyes with retinal degeneration
Vol.54:Measuring ion concentration in solutions for clinical and environmental research
Vol.55:Diabetic kidney disease: new biomarkers improve the prediction of the renal prognosis
Vol.56:New device for assisting accurate hemodialysis catheter placement
Vol.57:Possible link between excess chewing muscle activity and dental disease
Vol.58:Insights into mechanisms governing the resistance to the anti-cancer medication cetuximab
Vol.59:Role of commensal flora in periodontal immune response investigated
Vol.60:Role of commensal microbiota in bone remodeling
Vol.61:Mechanical stress affects normal bone development
Vol.62:3D tissue model offers insights into treating pancreatic cancer
Vol.63:Promising biomarker for vascular disease relapse revealed
Vol.64:Inflammation in the brain enhances the side-effects of hypnotic medication
Vol.65:Game changer: How do bacteria play Tag ?
Vol.66:Is too much protein a bad thing?
Vol.67:Technology to rapidly detect cancer markers for cancer diagnosis
Vol.68:Improving the diagnosis of pancreatic cancer
Vol.69:Early gastric cancer endoscopic diagnosis system using artificial intelligence
Vol.70:Prosthetics for Retinal Stimulation
Vol.71:The nervous system can contribute to breast cancer progression
Vol.72:Synthetic compound provides fast screening for potential drugs
Vol.73:Primary intraocular lymphoma does not always spread to the central nervous system
Vol.74:Rising from the ashes—dead brain cells can be regenerated after traumatic injury