DST-NFTHM Center National Facility for Tribal and Herbal Medicine

Institute of Medical Sciences, Banaras Hindu University

Motto of Government of India for establishment of this Center:

“The rapidly changing economic, trade and intellectual property scenario, nationally and internationally poses many challenges including the challenge of becoming leaders and competitors globally. This necessitates a shift in the approach of pharmaceutical industry to move away from manufacturing only known drugs through innovative process routes to discovering and commercializing new molecules. The accumulated knowledge of traditional medicinal system and large bio-diversity of our country offer a great advantage to drug industry. However, at present, most of the Indian drug firms, due to their small size compared to international operators, are not in a position to invest in a viable new drug development programme - drug development being a risky, resource intensive & time consuming process. At the same time several Indian academic institutions and national laboratories have established impressive infrastructure and developed excellent expertise in selected areas of drug development. Thus, this is a strong case for industry- institution interaction." With this motto, Govt. of India established this National Facility (National Facility for Tribal and Herbal Medicine) at Banaras Hindu University.

The center is working for advance research in area of drug development by taking the leads from ancient concept of Indian System of Herbal Medicine specifically indigenous tribal medical knowledge. For the establishment of this center, in 2008 DST granted facility entitled “Establishment of National facilities for Identification, Chemical characterization, Standardization and Quality Control of Medicinal Plants found in Tribal area in Central India” by sanctioning 7.56 Crore. After UGC approval the center is now

taken over by BHU w.e.f. 01.04.2013 through XII FYP of University vide UGC letter F.30.15/2007 (CU) dated 27 December, 2012.

Genesis: The importance of medicinal plants in traditional healthcare practices, providing clues to new areas of research and in biodiversity conservation is now well recognized. However, information on the uses for plants for medicine is lacking from many interior areas of tribal area of central India. Keeping this in view and accounting the ongoing research activities of Banaras Hindu University in the field of tribal and ayurvedic medicine research through BHU-UGC centre for the last more than 15 years, the DST-NFTHM Center has been established at Institute of Medical Sciences in order to excel the potential and its promotion in national interest. The biological standardization of herbal formulations for their therapeutic potential includes preclinical and clinical studies. Under current phase, the facilities for the research and clinical trial studies on Tribal & Herbal formulation for the prevention & management of neurodegenerative disorders, sleep disorders, diabetes mellitus, metabolic syndrome, obesity, menopausal syndrome have been established and the clinical trial studies as per ethical and regulatory norms are under progress.

Prime Objectives of National Facility

1. To conduct research for evaluation of therapeutic efficacy of Tribal Plants found in Central India.

2. To carry out identification, chemical characterization, standardization and quality control of medicinal plants found useful in different disorders such as cardiovascular, type-2 diabetes mellitus, neurodegenerative disorders, menopause etc.

3. To develop new investigational drug for clinical conditions taking leads from Tribal medical knowledge system.

4. To protect Intellectual Property Rights generated out of Tribal leads

5. Promotion of Intellectual Property Rights (IPRs) generated out of research outcomes.

6. Global promotion of Tribal Medicine by regulatory acceptance.

Detail information at www.nfthmimsbhu.webs.com

Brief information of Establishment

Units of DST-NFTHM Center-

Unit -1 Neurodegenerative study and Sleep Laboratory

In this unit various equipments especially for the electrophysiological investigations of the patients (study subjects) have been established. All the equipments are specific to the study pertaining to the neurodegenerative study and for sleep disorder study. All equipments are established in the facility are as per GLP standards for the investigations.

The major equipments installed in the facility along with brief details are as below:

1. Neuroperfect plus (EMG-2000-1) - The unit is established to observe the various type of changes in Nerve Conduction velocity of body of study subjects. The data taken in the form of MNCV, SNCV, VEP, H-reflex etc provide the information for the determination of neuro-degeneration of study cases. The machine if fully computerized and software based for functioning.

2. Sleepcare Polysomnography Machine (32 Channel) - Polysomnography is used in diagnosing and treating many sleep disorders, including neurologic disorders, movement disorders and importantly in the diagnosis of breathing disorders during sleep (sleep apnea).

3. Multiparameter Monitor- To check the different physical parameters of subjects such as Pulse, BP, PaO2, Temp etc the facility is established.

4. Digital Memory Scope - For checking the short time and long time memory power, the small portable equipment is installed. The serial learning and paired learning program installed in the instrument is being utilized to check the potential of study subjects. The easy technique to check the memory is available in this unit.

5. Transcranial Doppler Unit - Transcranial Doppler (TCD) is a test that measures the velocity of blood flow through the brain's blood vessels. Used to help in the diagnosis of emboli, stenosis, vasospasm from a subarachnoid hemorrhage (bleeding from a ruptured aneurysm), and other problems, this relatively quick and inexpensive test is growing in popularity in the United States. The equipment is fully computerized and software based having data storage potential.

6. Attention Span apparatus - Attention span is the amount of time that a person can concentrate on a task without becoming distracted. For evaluating the attention potential the equipment is fully computerized and has feasibility to store the data for the studies.

7. TMT machine - To check the abnormalities and changes during the physical exertion the machine records the data.

8. Computerised 32 channel EEG Analyzer (NV3200) - The machine measures the brain waves with help of 32 channels positioned on head of subject. The collected information in the form of EEG graph of study subjects usually provide the neurodegenerative changes in the brain. The machine is fully computerized and well equipped for data storage.

9. CDE machine- The unit is an advance automated unit for the detection of several electromagnetic waves of neurons in the body.

10. ENG Machine- The unit is an advance automated unit for the detection of several electromagnetic waves of neurons in the body.

11. Computerised Brain map (CBM2009) - The machine is highly sensitive for the electromagnetic changes of human brain. 32 electrodes positioned on the head of

subject collect specific information for development of Brain Maps like Voltage map, Frequency map and EEG graphs. The biochemical changes in human brain due stress or other responsible parameters can be visualized in the form of changes in voltage map. The facility is an important component of Neurodegenaraitive Study Unit.

12. Physiopac-4 Channel polygraph machine - Several of the electrophysiological characteristics of the human body can be measured with this machine. The test available with this machine are Electro-cephalogram (EEG), Electro-myogram (EMG), Occipital frontalis muscle action potential (ENG), Galvanic Skin Resistance (GSR), Pulse, Temperature etc. of study subjects. The machine is fully computerized and the recorded data of the patients are automatically stored in the Unit.

Unit-2 Drug Trial & Clinical Pathology Lab-

In this unit various equipments specific to the biochemical investigation, hematological study and urine analysis of the cases are regularly being done on GLP principles. All the equipments are specific to the study pertaining to the clinical pathology and are fully automated. The quality controls of equipments are adequate to the regulatory norms and are as per the required standards. The major equipments installed in the facility along with brief details are as below:

1. Fully Automated Biochemistry Analyzer (Cobas Integra 400/Roche) - The unit is established to measure different chemicals and other characteristics in a number of biological samples quickly. It is fully automated and properly quality controlled. These measured biochemistry tests of blood and other fluids may be useful in the evaluation of therapeutic potential of trial drugs.

2. Fully Automated 5 parts Haematology Analyzer (Celltac E) - The haematology analyser simultaneously measures 22 parameters including WBC 5- Part Differential. WBC, RBC and Platelet are measured by electrical resistance detection method. WBC is differentiated in to Neutrophil, Lymphocyte, Monocyte, Eosinophil and Basophil by light scatter technique (FLOW CYTOMETRY with laser).

3. Flow Cytometer: BD FACSCalibur: Flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second. This unit is in process to standardize various markers.

4. Fully Automated ELISA (Evidence Investigator, CLIA) - The Randox unit had been installed in the facility with a developed patented biochip array technology to enable the simultaneous determination of a panel of analytes from a single test sample. The evidence automated immunoassay analyser facilitates a very rapid throughput of test results per hour (capacity >2000 tests/hour possible). A wide range of biochip panels are available to test thyroid hormones, cytokines, tumour markers, fertility hormones and cardiac markers which are generally specific to human diagnostics.

5. Fully Automated Urine Analyzer (Cobas U 411/Roche) - This analyser is based on the principle of reflectance photometry. Test M calibration strips are used for the calibration of the photometer unit of the analyser and for quality control use commercially available Urine controls or other suitable control material were used. The unit is fully automated and well maintained for the required purpose.

6. Other supporting equipments like Autoclave, Centrifuge, Hot Air Oven, Water purification equipment, deep freeze are installed in the unit.

Unit-3 Immuno-Pathology Laboratory

The Immuno-pathology Lab has been developed in collaboration with UGC Advanced Immunodiagnostic Centre of the Department of Pathology, IMS, BHU. The following major equipments are procured and established under National facility for Tribal & Herbal Medicine scheme-

1. ELISA Reader - ELISA reader instrument is installed to do spectro-photometry in which they emit light at one wave length, and measure the amount of light absorbed and reflected by an object such as a protein. A spectrophotometer measures ultraviolet and visible light. Additionally, ELISA plate readers can also measure fluorescence and luminescence. Chemical dyes fluoresce or emit one color or wavelength when exposed to light. The amount of reflection, absorption and the color identify, and measure the amount of a substance.

2. Electrophoresis - Electrophoresis involves the separation of chemicals along a solid medium in the presence of an applied potential difference. In electrophoresis, chemicals such as blood proteins, DNA or inorganic ions can be separated according to differences in their mass and/or charge. The solid medium used in electrophoresis is usually an agarose or polyacrylamide gel.

3. -80°C, Deep Freezer - To store the blood samples and kits at low temperature the facility is established.

4. Trinocular & Binocular Microscope - These advance microscope facilities are equipped with PC to collect the images of slides.

5. Cryostat Microtome - The facility is installed for sectioning of tissues at very low temperature.

6. Immuno-fluorescent Microscope - This advance immune florescent microscope facilities are equipped with PC to collect the images of slides.

7. Mini PCR - Polymerase chain reaction unit is established in the lab to amplify small quantity of DNA.

8. Real Time PCR - Real-time polymerase chain reaction, also called quantitative real time polymerase chain reaction (Q-PCR/qPCR/qrt-PCR) or kinetic polymerase chain reaction (KPCR), is a laboratory unit based on the PCR, which is used to amplify and simultaneously quantify a targeted DNA molecule. It enables both detection and

quantification (as absolute number of copies or relative amount when normalized to DNA input or additional normalizing genes) of one or more specific sequences in a DNA sample. 9. Inverted Microscope - The instrument is another microscope for routine sample study.

10. Cryo Centrifuge - The low temperature fully automated centrifuge is established in the facility.

11. Other instruments like Freeze, incubators, and other lab units are available in the facility.

Unit-4 Record and Archival Unit-

As per regulatory requirement, this unit has been developed, where all the records; case sheets, register, relevant documents etc. will be preserved. Hard copy and soft copy are also being preserved for next 15 years as per regulatory requirement. In order to ensure there is no way that these records are destroyed. All the relevant SOPs are for archival records have been developed.

Unit-5 Field Trial Unit-

Field Trial Unit has been established and is in operation as per international regulatory requirement with the following aspects- To conduct the epidemiological survey of the local population with special reference to health seeking behavior, nutrition, common relevant disease and for screening of target patient for clinical trial. The unit is equipped with basic equipments like Height and weight machine, skill, Blood Pressure Monitoring Machine, Anthropometric tape, necessary furniture etc. This group has also established regular field OPD’s on various days (working or off days) in different areas of rural and city area.

Unit- 6 Herbal Drug Quality Validation Unit-

As per regulatory requirement this unit is being developed for the analysis and research for the evaluation of marker compounds in herbal drugs (plants), their quality validation and investigation of newer chemical entities in tribal and herbal plants. The objectives of the unit is validation and record of raw drugs along with their pharmacognosy, collection and review of literature from ancient to modern period related to drugs, management of the quality of drugs. The exploration of tribal medical practices resided in the rural and tribal communities of this part of country is being done through visits in these areas and the practices are being standardized for collection of traditional medical knowledge. The regular testing of herbal formulations and ayurvedic drugs are being processed in Ayurvedic pharmacy. In addition to experimental setup the facility of specific HPLC-PDA unit is in process of procurement for the quantitative evaluation of active principles of herbal drugs and formulations.

Unit-7 GCP Complied Metabolic Ward and OPD Unit-

GCP complied metabolic ward for proper observation of serious patients and study patients; a specific six bedded metabolic ward have been developed at Sir Sunderlal Hospital, Banaras Hindu University. This ward is fully supported by Coronary Care Unit, Intensive Care Unit and Emergency backup of Sir Sunderlal Hospital. The patients if required are being admitted under Co-coordinator for definite management.

For follow up, special O.P.D. are running in Room No.219 from 08:00 AM to 2:30 PM on every Tuesday, Thursday (Room No.219 ) and in Ayurveda OPD where in addition to consultation, patients are being investigated for the disorders and registered in specific clinical trial studies.

For follow up and recruitment of cases in different group, special O.P.D. are running in from 08:00 AM to 2:30 PM on every Tuesday, Thursday (OPD No.219) and Wednesday, Thursday (Ayurveda Kaya-chikkitsha).

Unit-8 Nutritional and Yogic intervention Unit-

Specialized group nutritional and yogic experts are involved to provide a cost-effective

way of treating patients with chronic or recurrent life style disorders along with the

benefits of yoga. The minimized cost assumed for yoga intervention is important in

determining whether this is an efficient use patient in controlling disorders. The research

data are in correlation for augmented effect of these interventions. This unit is working

in this area.

Unit-9 Quality Control Assurance Unit-

As per GLP guidelines and International requirements Quality Assurance is an important aspect for any facility of clinical trial. In our National facility this is headed by a Quality Assurance Director and two expert assistants are working for QA. This unit is responsible for monitoring the activities of all levels both on schedule and off schedule. The detail working protocol and SOPs for this unit has been developed.

Contact information

Nodal Officer: Director, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, UP India E-Mail: directorims@gmail.com Call at: (O) 91-542- 2367568, (R) 91-542-2369936, (M) 91-9839080939

DST-NFTHM Center:

Scientist Dr. Satya Prakash, M.Sc. Ph.D. E.Mail: satya_res2004@yahoo.co.in, Cell: 9415812128

Medical Officer:

Dr. Sushama Tiwari, M.D., MRAV (Delhi), Ph.D (BHU)

Cell: 9415221538Dr. Praveen Kumar Singh, B.Sc., BAMS, Dip. Yoga (BHU) Email: praveensingh.bhu@gmail.com Cell: 9415356798

Computer Programmer:

Rajeev Kumar Dubey, MCA

Email: dubey.friend@gmail.com, dubey_friends@yahoo.com Cell: 9307079491, Junior Research Fellow

Minakshi Dwivedi, Abhishek Kumar, Papinder Singh

Technical Assistants

Ms. Shailja Singh, Naresh Kumar Mishra, Neetu Gupta

Field Attendant

Peer Muhammad

Office/ Animal Attendant

Manoj Patel

Ward Sahayak

Mrs. Rinku Singh, Mr. Dhananjay Srivastava Mrs Chanda Devi

Safaiwala

Mamta, Najim, Vishnu

Peon

Mr. Arvind Kumar Sharma

Achievements and IPRs (Patents) & Future Plans-

National and International patents-

i. Herbal preparation for management of cardiovascular and neurological disorders and to a process for the preparation there of EP Patent no.1569 666.

ii. Neuropsychiatric and cardiovascular complications among menopausal women. Patent no. 851 DEL 2007.

iii. Prevention and management of cognitive decline among aged – Patent no.715 DEL 2002.

iv. An herbal formulation for the prevention and management of potential diabetes and a process for preparation thereof – Patent no. 664 DEL 2002, 43 28.

v. An herbal preparation for the prevention and management of hyperchlorosterolemia and hypertriglyceridemia and a process for preparation thereof – Patent no. 662 DEL 2002.

vi. An herbal formulation for the treatment of arthritis – a process for the preparation thereof – Patent no. 317 DEL 2002.

vii. An herbal composition for the management of pre-menopausal syndrome and a process or preparation there of Patent no. 714 DEL 2002.

viii. Role of the combined formulation “Salacia chinensis, Hippophae rhamnoides and Coccinia indica” in the prevention and management of type-II diabetes mellitus including its micro-vascular complications Patent no. IN 2005/000223.

ix. Role of Hippophae rhamnoides in the management of hyperhomocysteinemia and other risk factors associated with coronary heart disease. Patent no. 704 KOL 2006.

x. Clinical application of Salacia oblonga and its significance in the prevention of micro-vascular complications in type-II diabetes mellitus cases. Patent no. 314 CHE 2007.

Plans of National Facility:

1. Development of Research lab for Experimental studies: In the current phase, the preclinical experimental studies for tribal formulation are being done in collaborative centres in India. In future program we have to establish a GLP Research Lab for experimental studies under this National facility centre. For building component the Dept. of AYUSH has given his consent.

2. GLP accreditation of established facilities by regulatory authorities: The regulatory acceptance of drug development research is mandatory for global promotion of tribal and herbal drug. The GLP accreditation of established facilities is urgent and is under process.

3. Conduction of training program for GLP and Drug development research of Tribal Medicine: As per the DST recommendations the regular programs for training for GLP and Tribal Drug Development will be conducted for exploration and development of expertise.

4. Exploration of new investigational tribal and herbal drugs taking the leads from existing knowledge in tribal community of central India: The Tribes of India have preserved a rich national heritage in the form of Tribal medicine. The tribal populations, who have been the primary inhabitants of natural habitats, hold tremendous amount of traditional knowledge on the use of various biotic resources, which may have greater importance to the on-going research and discoveries in the field. The Tribes are living in a closed compact society and utilizing plants and animal materials found in their locality. The compilation of the traditional concepts and the development of new formulations after taking the leads from tribal medical knowledge will be explored from this part of the country which will be certainly a key mandate of this establishment.

5. Clinical Trial studies for the AYUSH ayurvedic formulation: The GLP and GCP complied clinical trial studies will be undertaken by the National facility of known AYUSH ayurvedic formulation for regulatory global acceptance.

6. Area of collaboration and interest: These research facilities are open for all the research workers and scientists who are working in the area of tribal and herbal medicine to take advantage of facilities in developing tribal and herbal drug for global promotion.