Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects

Tawit Suriyo; Nanthanit Pholphana; Teerapat Ungtrakul; Nuchanart Rangkadilok; Duangchit Panomvana; Apinya Thiantanawat; Wanwisa Pongpun; Jutamaad Satayavivad

doi:10.1055/s-0043-104382

Planta Medica, Table of Contents

Planta Med 2017; 83(09): 778-789
DOI: 10.1055/s-0043-104382

Biological and Pharmacological Activity

Original Papers

Clinical Parameters following Multiple Oral Dose Administration of a Standardized Andrographis paniculata Capsule in Healthy Thai Subjects

Authors

Tawit Suriyo

¹Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

²Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand
Nanthanit Pholphana

¹Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand
Teerapat Ungtrakul

³Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
Nuchanart Rangkadilok

¹Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

²Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand

⁴Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand
Duangchit Panomvana

⁵Translational Research Unit, Chulabhorn Research Institute, Bangkok, Thailand
Apinya Thiantanawat

¹Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

²Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand

⁴Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand
Wanwisa Pongpun

³Chulabhorn Hospital, Chulabhorn Royal Academy, Bangkok, Thailand
Jutamaad Satayavivad

¹Laboratory of Pharmacology, Chulabhorn Research Institute, Bangkok, Thailand

²Center of Excellence on Environmental Health and Toxicology, Office of Higher Education Commission, Ministry of Education, Bangkok, Thailand

⁴Chulabhorn Graduate Institute, Chulabhorn Royal Academy, Bangkok, Thailand

Abstract

Andrographis paniculata has been widely used in Scandinavian and Asian counties for the treatment of the common cold, fever, and noninfectious diarrhea. The present study was carried out to investigate the physiological effects of short-term multiple dose administration of a standardized A. paniculata capsule used for treatment of the common cold and uncomplicated upper respiratory tract infections, including blood pressure, electrocardiogram, blood chemistry, hematological profiles, urinalysis, and blood coagulation in healthy Thai subjects. Twenty healthy subjects (10 males and 10 females) received 12 capsules per day orally of 4.2 g of a standardized A. paniculata crude powder (4 capsules of 1.4 g of A. paniculata, 3 times per day, 8 h intervals) for 3 consecutive days. The results showed that all of the measured clinical parameters were found to be within normal ranges for a healthy person. However, modulation of some parameters was observed after the third day of treatment, for example, inductions of white blood cells and absolute neutrophil count in the blood, a reduction of plasma alkaline phosphatase, and an induction of urine pH. A rapid and transient reduction in blood pressure was observed at 30 min after capsule administration, resulting in a significant reduction of mean systolic blood pressure. There were no serious adverse events observed in the subjects during the treatment period. In conclusion, this study suggests that multiple oral dosing of A. paniculata at the normal therapeutic dose for the common cold and uncomplicated upper respiratory tract infections modulates various clinical parameters within normal ranges for a healthy person.

Key words

Andrographis paniculata - Acanthaceae - blood pressure - blood chemistry - hematological profiles - urinalysis - electrocardiogram

Full Text

References

References
1 Yelne MB, Sharma PC, Dennis TJ. Bhunimba: Andrographis paniculata (Burm. F.) Wall. ex Nees. In: Sharma PC, Yelne MB, Dennis TJ, Joshi A. eds. Database on medicinal Plants used in Ayurveda, Vol. 4. New Delhi: Central Council for Research in Ayurveda & Siddha; 2002: 34-60
2 Chinese Pharmacopoeia Commission. Herba Andrographis (Chuanxinlian). In: Chinese Pharmacopoeia Commission. ed. Pharmacopoeia of the Peopleʼs Republic of China, Vol. 1. (English ed.). Beijing: China Medical Science; 2010: 32-33
3 Department of Medical Sciences. Andrographis Herb. In: Department of Medical Sciences. ed. Thai Herbal Pharmacopoeia, Vol. 1. Bangkok: Prachachon; 1995: 24-31
4 National Drug Committee. List of herbal medicinal Products A.D. 2006. Bangkok: Agricultural Cooperative Community of Thailand; 2006: 18-19
5 World Health Organization. Herba Andrographidis. In: World Health Organization. ed. WHO Monographs on selected medicinal Plants, Vol. 2. Geneva: World Health Organization; 2004: 12-24
6 Pholphana N, Rangkadilok N, Thongnest S, Ruchirawat S, Ruchirawat M, Satayavivad J. Determination and variation of three active diterpenoids in Andrographis paniculata (Burm.f.) Nees. Phytochem Anal 2004; 15: 365-371
7 Pholphana N, Rangkadilok N, Saehun J, Ritruechai S, Satayavivad J. Changes in the contents of four active diterpenoids at different growth stages in Andrographis paniculata (Burm.f.) Nees (Chuanxinlian). Chin Med 2013; 8: 2
8 Cheung HY, Cheung CS, Kong CK. Determination of bioactive diterpenoids from Andrographis paniculata by micellar electrokinetic chromatography. J Chromatogr A 2001; 930: 171-176
9 Akbar S. Andrographis paniculata: a review of pharmacological activities and clinical effects. Altern Med Rev 2011; 16: 66-77
10 Chua LS. Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection. Phytother Res 2014; 28: 1589-1598
11 Hossain MS, Urbi Z, Sule A, Hafizur Rahman KM. Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacology. ScientificWorldJournal 2014; 2014: 274905
12 Lim JC, Chan TK, Ng DS, Sagineedu SR, Stanslas J, Wong WS. Andrographolide and its analogues: versatile bioactive molecules for combating inflammation and cancer. Clin Exp Pharmacol Physiol 2012; 39: 300-310
13 Suriyo T, Pholphana N, Rangkadilok N, Thiantanawat A, Watcharasit P, Satayavivad J. Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis. Planta Med 2014; 80: 533-543
14 Caceres DD, Hancke JL, Burgos RA, Wikman GK. Prevention of common colds with Andrographis paniculata dried extract. A pilot double blind trial. Phytomedicine 1997; 4: 101-104
15 Caceres DD, Hancke JL, Burgos RA, Sandberg F, Wikman GK. Use of visual analogue scale measurements (VAS) to assess the effectiveness of standardized Andrographis paniculata extract SHA-10 in reducing the symptoms of common cold. A randomized double blind-placebo study. Phytomedicine 1999; 6: 217-223
16 Hancke JL, Burgos RA, Caceres DD, Wikman G. A double-blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds. Phytother Res 1995; 9: 559-562
17 Melchior J, Palm S, Wikman G. Controlled clinical study of standardized Andrographis paniculata extract in common cold – a pilot trial. Phytomedicine 1997; 3: 315-318
18 Melchior J, Spasov AA, Ostrovskij OV, Bulanov AE, Wikman G. Double-blind, placebo-controlled pilot and phase III study of activity of standardized Andrographis paniculata Herba Nees extract fixed combination (Kan jang) in the treatment of uncomplicated upper-respiratory tract infection. Phytomedicine 2000; 7: 341-350
19 Thamlikitkul V, Dechatiwongse T, Theerapong S, Chantrakul C, Boonroj P, Punkrut W, Ekpalakorn W, Boontaeng N, Taechaiya S, Petcharoen S. Efficacy of Andrographis paniculata, Nees for pharyngotonsillitis in adults. J Med Assoc Thai 1991; 74: 437-442
20 Chuthaputti A, Pornpatkul V, Suwankiri U. The efficacy of Andrographis paniculata (Burm. f.) Wall. ex Nees for the relief of the symptoms of influenza. J Thai Trad Alter Med 2007; 5: 257-265
21 Burgos RA, Caballero EE, Sanchez NS, Schroeder RA, Wikman GK, Hancke JL. Testicular toxicity assessment of Andrographis paniculata dried extract in rats. J Ethnopharmacol 1997; 58: 219-224
22 Coon JT, Ernst E. Andrographis paniculata in the treatment of upper respiratory tract infections: a systematic review of safety and efficacy. Planta Med 2004; 70: 293-298
23 Pholphana N, Panomvana D, Rangkadilok N, Suriyo T, Ungtrakul T, Pongpun W, Thaeopattha S, Satayavivad J. A simple and sensitive LC-MS/MS method for determination of four major active diterpenoids from Andrographis paniculata in human plasma and its application to a pilot study. Planta Med 2016; 82: 113-120
24 Pholphana N, Panomvana D, Rangkadilok N, Suriyo T, Puranajoti P, Ungtrakul T, Pongpun W, Thaeopattha S, Songvut P, Satayavivad J. Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers. J Ethnopharmacol 2016; 194: 513-521
25 Yoopan N, Thisoda P, Rangkadilok N, Sahasitiwat S, Pholphana N, Ruchirawat S, Satayavivad J. Cardiovascular effects of 14-deoxy-11,12-didehydroandrographolide and Andrographis paniculata extracts. Planta Med 2007; 73: 503-511
26 Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S, Satayavivad J. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation. Eur J Pharmacol 2006; 553: 39-45
27 Zhang CY, Tan BK. Hypotensive activity of aqueous extract of Andrographis paniculata in rats. Clin Exp Pharmacol Physiol 1996; 23: 675-678
28 Jain B, Raghuwanshi R. Phytochemical and pharmacological evaluation of leaves of Andrographis paniculata for hypoglycemic activity. Asian J Biochem Pharm Res 2014; 4: 53-59
29 Amroyan E, Gabrielian E, Panossian A, Wikman G, Wagner H. Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation. Phytomedicine 1999; 6: 27-31
30 Babayi HM, Udeme JJ, Abalaka JA, Okogun JI, Salawu OA, Akumka DD, Adamu. Zarma SS, Adzu BB, Abdulmumuni SS, Ibrahime K, Elisha BB, Zakariys SS, Inyang US. Effect of oral administration of aqueous whole extract of Cassytha filiformis on haematograms and plasma biochemical parameters in rats. J Med Toxicol 2007; 3: 146-151
31 Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S. Anticancer and immunostimulatory compounds from Andrographis paniculata . J Ethnopharmacol 2004; 92: 291-295
32 Naik SR, Hule A. Evaluation of immunomodulatory activity of an extract of andrographolides from Andrographis paniculata . Planta Med 2009; 75: 785-791
33 Puri A, Saxena R, Saxena RP, Saxena KC, Srivastava V, Tandon JS. Immunostimulant agents from Andrographis paniculata . J Nat Prod 1993; 56: 995-999
34 Radhika P, Annapurna A, Rao SN. Immunostimulant, cerebroprotective & nootropic activities of Andrographis paniculata leaves extract in normal & type 2 diabetic rats. Indian J Med Res 2012; 135: 636-641
35 Bukoye O, Musbau A. Immune modulation potential of aqueous extract of Andrographis paniculata leaves in male rat. Researcher 2011; 3: 48-57
36 Yasuda Y, Ishida K, Miyamura M. Effects of blood gas, pH, lactate, potassium on the oxygen uptake time courses during constant-load bicycle exercise. Jpn J Physiol 1992; 42: 233-237
37 Akdogan M, Ozguner M, Aydin G, Gokalp O. Investigation of biochemical and histopathological effects of Mentha piperita Labiatae and Mentha spicata Labiatae on liver tissue in rats. Hum Exp Toxicol 2004; 23: 21-28
38 Siest G, Galteau MM, Malya PA, Tryding N, Delwaide P, Salway JG, Tognoni G. International Federation of Clinical Chemistry, Scientific Committee: Drug interferences and drug effects in clinical chemistry. Part 3. Evaluation of biological effects of drugs. J Clin Chem Clin Biochem 1988; 26: 169-173
39 Krones E, Erwa W, Trauner M, Fickert P. Serum alkaline phosphatase levels accurately reflect cholestasis in mice. Hepatology 2015; 62: 981-983
40 Singh P, Srivastava MM, Khemani LD. Renoprotective effects of Andrographis paniculata (Burm. f.) Nees in rats. Ups J Med Sci 2009; 114: 136-139
41 Nayeem F, Anderson KE, Nagamani M, Grady JJ, Lu LJ. Alkaline phosphatase and percentage body fat predict circulating C-reactive protein in premenopausal women. Biomarkers 2010; 15: 663-670
42 Australian Government, Department of Health, Therapeutic Goods Administration. Safety review of Andrographis paniculata and anaphylactic/allergic reactions. Version 1.0, October 2015. Available at. https://www.tga.gov.au/sites/default/files/safety-review-andrographis.pdf Accessed January 11, 2017

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