Journal of Ethnopharmacology 171 (2015) 1–3

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Ethnopharmacological communication

Antacid activity of Laportea aestuans (L.) Chew Charlotte Bremer Christensen a, Jens Soelberg a,b, Anna K. Jäger a,n a b

Department of Drug Design and Pharmacology, Universitetsparken 2, 2100 Copenhagen, Denmark Museum of Natural Medicine, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark

art ic l e i nf o

a b s t r a c t

Article history: Received 7 April 2015 Received in revised form 16 May 2015 Accepted 17 May 2015 Available online 25 May 2015

Ethnopharmacological relevance: Laportea aestuans (L.) Chew (Urticaceae) was historically ingested together with chalk by pregnant women in Ghana when suffering from heartburn. The aim of this study was to evaluate the antacid activity of the aerial parts of L. aestuans. Materials and methods: Aerial parts of L. aestuans were collected in the Accra region of Ghana. The antacid activity was measured according to Fordtran's titration model. 90 mL tap water and test material in a 500 mL beaker were warmed to 37 1C on a magnetic stirrer and was continuously stirred at approximately 30 rpm in order to mimic the movements of the stomach. A titration was carried out with an artificial gastric acid to the end point of pH 3. The acid secretion rate was approximately 3 mL and pH was monitored with a pH meter. Concentrations of 666 and 1332 mg dried plant material were tested, both with and without addition of calcium carbonate (CaCO3). Results: Both CaCO3 and L. aestuans had a significant better ability than water to neutralise an artificial stomach acid. 666 mg plant material together with CaCO3 compared to CaCO3 alone showed approximately the same neutralisation time. When mixing 1332 mg plant material with CaCO3 the neutralisation time was significantly higher than for CaCO3 alone and exhibited an antacid profile that was able to maintain the neutralising activity one pH-unit higher for an extended period of time. Conclusion: The results indicate that L. aestuans showed an antacid activity when combined with CaCO3. With further investigations of the active compound, mechanism of action and possible toxicity, the plant could form the basis of a novel antacid. & 2015 Elsevier Ireland Ltd. All rights reserved.

Keywords: Antacid activity Laportea aestuans (L.) Chew Medicinal plant

1. Introduction The antacid study of the medicinal plant Laportea aestuans (L.) Chew (Urticaceae) is a part of a larger research collaboration, which is aimed at examining ‘forgotten medicinal plants’ in Ghana (Soelberg et al., 2015). In 1817, Henry Tedlie, participating in Bowdich's expedition from the Cape Coast to the Ashanti capital Kumasi, recorded that L. aestuans was used as an antacid (Bowdich, 1819). L. aestuans has later been recorded used for other ailments in West Africa, but appears to have fallen out of use in Ghana for any ailments (Soelberg et al., 2015). During pregnancy women may suffer from acid dyspepsia and experience symptoms such as heartburn and nausea (Strugula et al., 2012). Historically, the plant L. aestuans was ingested by pregnant women, who suffered from heartburn. The plant was prepared by crushing it, mixing it with chalk and then drunk (Bowdich, 1819). Approximately 30–40% of adults experience dyspepsia (Harmon and Peura, 2010). Acid dyspepsia is the condition when

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Corresponding author. Tel.: þ 45 35336339; fax: þ45 35336041. E-mail address: [email protected] (A.K. Jäger).

http://dx.doi.org/10.1016/j.jep.2015.05.026 0378-8741/& 2015 Elsevier Ireland Ltd. All rights reserved.

the stomach produces excess gastric acid. The symptoms of dyspepsia originate from the upper gut and may consist of nausea, vomiting, heartburn, flatulence, reflux, ulcer, restlessness or decreased appetite (Harmon and Peura, 2010; Panda and Khambat, 2013; Sandhya et al., 2012; Sharma et al., 2012). The cause of dyspepsia can be due to peptic ulcer disease (with or without the bacteria Helicobacter pylori), duodenitis, gastritis, use of some types of medicine, gastro-oesophageal reflux disease (GORD) or functional dyspepsia (Harmon and Peura, 2010; Panda and Khambat, 2013; Sandhya et al., 2012). Previously, a number of other plants have been tested for antacid activity. The root of Tephrosia purpurea (L.) Pers were tested in vitro with the modified Vatier's artificial stomach model in order to measure the antacid activity in methanol, ethyl acetate and chloroform extracts. The methanolic extract had a higher antacid activity than sodium bicarbonate, whereas the other two extracts showed moderately good response, but less than the standard (Sandhya et al., 2012). Aqueous extracts of the fruit rind of Garcinia indica was tested for its antacid activity also using the modified Vatier's artificial stomach model. The extracts showed potent antacid activity when compared to water, but not as good as the standard sodium bicarbonate (Panda and Khambat, 2013).

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C.B. Christensen et al. / Journal of Ethnopharmacology 171 (2015) 1–3

Palestinian folk medicinal herbs were tested for their antacid activity by adding excess acid and followed by a back-titration of the excess acid with sodium hydroxide. In comparison to magnesium hydroxide and calcium carbonate tablets the medicinal herbs did not show any significant antacid activity (Houshia et al., 2012). L. aestuans (L.) Chew, with the historical name of ‘hooghong' and the modern Akan name ‘hunhon’, is an annual herb which can grow up to 1–3 m long. It is a very common pantropical plant and often considered a weed, has fleshy stem, woody at the base, few branches and covered with stinging/non-stinging hairs 1–3 mm long (Brink, 2009; Burkill, 2000; Oloyede and Ayanbadejo, 2014). This antacid experiment was carried out to investigate if L. aestuans had an antacid activity, both with chalk (calcium carbonate) and alone. Antacid activity was defined as the ability to maintain the pH value above 3 when adding an artificial stomach acid with a pH of 1.2.

2. Methods and materials 2.1. Plant material Aerial parts of L. aestuans were collected in the Accra region of Ghana. The plant was identified and authenticated by ethnobotanist Jens Soelberg, University of Copenhagen, Denmark. Botanical voucher specimens were deposited at the herbaria at University of Ghana (GC), Ghana and, University of Copenhagen (C), Denmark under the accession number JS264. 2.2. Antacid activity assay Dried plant material was grinded in a coffee grinder. Each test sample (666 or 1332 mg plant material; 400 mg CaCO3; 666 or 1332 mg plant material with 400 mg CaCO3) in 90 mL tap water was placed in a 500 mL beaker and warmed to 37 1C. A magnetic stirrer was continuously run at approximately 30 rpm to mimic the movements of the stomach. All of the test samples were titrated with an artificial gastric acid (800 U/l pepsin (SigmaAldrich) in 34 mM NaCl, pH 1.20, adjusted with HCl) to the end point of pH 3 according to Fordtran's model (Fordtran et al., 1973). The acid secretion rate was set at approximately 3 mL/min (Panda and Khambat, 2013; Sandhya et al., 2012) by adding 750 mL every 15 s. pH was monitored with a pH meter and noted every minute. The end point was set at pH 3.00 to determine the gastric residence time (Sharma et al., 2012). All the tests were performed in triplicate.

2.3. Data All data were analysed by Microsoft Excel. The mean of the triplicate data were calculated and used as the final result. Standard deviations are noted in parentheses. An F-test and a Student's t-test were performed to check whether two sets of data were statistically different from each other.

3. Results and discussion There were no records of the amount originally used of the plant. We estimated that one or two teaspoons of grinded plant material were a dose, which could realistically be taken orally. One teaspoon of material weighted 666 mg. The dose of chalk (400 mg) was based on the dose administered clinically for antacidtreatment. Fig. 1 shows that both CaCO3 and L. aestuans had a significant better ability than water to neutralise the artificial stomach acid. The reference neutralising compound CaCO3 had a duration time of 48.92 ( 70.52) minutes. Plant material of L. aestuans in the amounts of 666 mg and 1332 mg had a duration of antacid activity of 7.67 ( 70.52) and 20.67 (70.38) min, respectively. This shows that when doubling the concentration of the plant material, the antacid activity was more than twice as effective. Importantly, when combining the plant material with CaCO3 the antacid profile exhibited an ability to maintain the neutralising activity one pHunit higher for an extended period of time. When mixing the 666 mg plant material with CaCO3 the duration time was 50.92 (70.88) min, which was approximately the same duration time as CaCO3 alone, though statistically different (Po 0.05). The duration time of 1332 mg plant material in combination with CaCO3 was 71.33 (70.52) minutes, which was over 22 min longer than for CaCO3 alone. This indicates that L. aestuans showed a significant antacid activity together with CaCO3, as it was historically ingested by pregnant women. In modern medicine there are a variety of different antacids, but many of them may cause adverse effects, drug interactions, can be expensive for the poor population and may have limitations when it comes to the duration of action. The antacids are often efficient, but can result in adverse effects such as altered bowel functions. Aluminium-based antacids can cause constipation whereas magnesium-based antacids can cause diarrhoea (Panda and Khambat, 2013; Sandhya et al., 2012). Sodium bicarbonate should be avoided because of the high amount of sodium, which could cause a systemic pH alteration and may generate large

Fig. 1. Antacid profiles of L. aestuans, CaCO3, and L. aestuans together with CaCO3. -●- Water, -  - CaCO3, -■- 666 mg L. aestuans, -◆- 1332 mg L. aestuans, -▲- 666 mg L. aestuans þ400 mg CaCO3 and -x- 1332 mg L. aestuansþ 400 mg CaCO3.

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amounts of carbon dioxide (Panda and Khambat, 2013; Sandhya et al., 2012; Walker and Whittlesea, 2012). Antacids may cause drug interactions with pH-dependent controlled-release medicine. Interactions also occurs between antacids and antibiotics such as tetracycline and ciprofloxacin (Sandhya et al., 2012; Walker and Whittlesea, 2012). Because of the side effects and drug interactions of antacids it might be worth considering medicinal plants such as L. aestuans as an alternative, or additive to reduce the amount of CaCO3 ingested. A Brazilian study described the plant as a remedy used to reduce symptoms of osteoporosis. A study from Cameroon confirmed that the plant was used against ‘low calcium’ (Jiofack et al., 2010). The free calcium concentration of the dry leaves was 638 mg/100 g (Oliveira et al., 2012), which means that the free calcium in the L. aestuans material in the high dose of 1.332 g is 8 mg, which cannot explain the improved antacid effect of the combined plant material and CaCO3. In order for L. aestuans to be considered as a basis for a novel antacid, the plant should be thoroughly tested for toxicity and potential adverse effects. Previous studies have already indicated that some compounds derived from the plant could be toxic. The essential oil from the whole plant gave a LC50 of 367 mg/mL, which indicated that the oil was toxic. The main constituent of the oil was methyl salicylate (54.5%) (Oloyede, 2011). Hexane, ethyl acetate and butanol extracts from L. aestuans all showed toxicity in the brine shrimp lethality test with LC50 of 0.0002, 57.2 and 117.8 mg/mL, respectively, whereas the methanolic extract was considered non-toxic with an LC50 of 1330.9 mg/mL (Oloyede and Ayanbadejo, 2014).

4. Conclusion Ground material of aerial parts of L. aestuans in combination with CaCO3 increased the antacidic effect by prolonging the effect and keeping the pH level at about one unit higher for most of the time period. Further detailed research has to be done in order to localise the neutralising compound in the plant and also to find the mechanism of action. More substantial toxicity investigations should be conducted to assess whether this plant can be used in modern phytomedicine. The use of L. aestuans as an antacid was recorded in 1817, but since then apparently forgotten. In this study, we showed that the plant material of L. aestuans possessed antacid activity. This demonstrates the value of documenting ethnopharmacological data, so knowledge on medicinal plants is not forgotten due to cultural changes over time. When recorded, ethnopharmacological

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data are both preservation of knowledge, but also a source for the future to find new therapies or restoring healing practices. Acknowledgements The project was funded by the Cand. pharm. Povl M. Assens Foundation, the Carlsberg Foundation (2012-01-0118) and Hjælpefonden for undergraduates, graduate students and graduates from School of Pharmaceutical Sciences at Faculty of Health and Medical Sciences. Thanks are given to Dr. Alex Asase and Mr. J.Y. Amponsah at Department of Botany, University of Ghana for their assistance. References Bowdich, T.E., 1819. Mission from Cape Coast Castle to Ashantee. Frank Cass & Co. Ltd, London. Brink, M., 2009. Laportea aestuans (L.) Chew. In: Brink, M., Achigan-Dako, E.G. (Eds.), Prota 16: Fibres/Plantes à Fibres. [CD-Rom].. PROTA, Wageningen, Netherlands. Burkill, H.M., 2000. The useful plants of West Tropical Africa. Families S–Z, second ed. Royal Botanic Gardens Kew, Richmond, Surrey. Fordtran, J.S., Morawski, S.G., Richardson, C.T., 1973. In vivo and in vitro evaluation of liquid antacids. N. Engl. J. Med. 1288, 923–928. Harmon, R.C., Peura, D.A., 2010. Evaluation and management of dyspepsia. Ther. Adv. Gastroenterol. 3, 87–98. Houshia, O.J., AbuEid, M., Zaid, O., Zaid, M., Al-daqqa, N., 2012. Evaluation of the effectiveness of the acid-neutralizing contents of selected Palestinian folk medicinal herbs. Adv. Pure Appl. Chem. 4, 77–79. Jiofack, T., Fokunang, C., Guedje, N., Kemeuze, V., Fongnzossie, E., Nkongmeneck, B. A, Mapongmetsem, P.M., Tsabang, N., 2010. Ethnobotanical uses of medicinal plants of ethnoecological regions of Cameroon. Int. J. Med. Med. Sci. 2, 60–79. Oliveira, G.L., Andrade, L.H.C., Oliveira, A.F.M., 2012. Xanthosoma sagittifolium and Laportea aestuans: species used to prevent osteoporosis in Brazilian traditional medicine. Pharm. Biol. 50, 930–932. Oloyede, G.K., 2011. Toxicity, antimicrobial and antioxidant activities of methyl salicylate dominated essential oils of Laportea aestuans (Gaud). Arab. J. Chem., 1. http://dx.doi.org/10.1016/j.arabjc.2011.09.019. Oloyede, G.K., Ayanbadejo, O.E., 2014. Phytochemical, toxicity, antimicrobial and antioxidant screening of extracts obtained from Laportea aestuans (Gaud). J. Med. Sci. 14, 51–59. Panda, V., Khambat, P., 2013. Evaluation of antacid activity of Garcinia indica fruit rind by a modified artificial stomach model. Bull. Env. Pharmacol. Life Sci. 2, 38–42. Sandhya, S., Venkata, R.K., Vinod, K.R., Chaitanya, R., 2012. Assessment of in vitro antacid activity of different root extracts of Tephrosia purpurea (L.) Pers by modified artificial stomach model. Asian Pac. J. Trop. Biomed. 2, 1487–1492. Sharma, S., Dwivedi, J., Paliwal, S., 2012. Evaluation of antacid and carminative properties of Cucumis sativus under simulated conditions. Der Pharm. Lett. 4, 234–239. Soelberg, J., Asase, A., Akwetey, G., Jäger, A.K., 2015. Historical versus contemporary medicinal plant uses in Ghana. J. Ethnopharmacol. 160, 109–132. Strugula, V., Bassin, J., Swales, V.S., Lindow, S.W., Dettmar, P.W., Thomas, E.C., 2012. Assessment of the safety and efficacy of a raft-forming alginate reflux suppressant (liquid gaviscon) for the treatment of heartburn during pregnancy. ISRN Obstet. Gynecol. 2012, 481870. Walker, R., Whittlesea, C., 2012. Clinical Pharmacy and Therapeutics. Churchill Livingstone, London.

Antacid activity of Laportea aestuans (L.) Chew.

Laportea aestuans (L.) Chew (Urticaceae) was historically ingested together with chalk by pregnant women in Ghana when suffering from heartburn. The a...
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