Medicinal uses, phytochemistry and biological activities of Ehretia obtusifolia Hochst. ex DC. (Ehretiaceae)


Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5770, South Africa, 0027719600326

Abstract

Ehretia obtusifolia Hochst. ex DC. is a shrub or small tree which occurs naturally in tropical Africa and Asia. This study aims to provide some information about the medicinal uses, phytochemistry and biological activities of E. obtusifolia. This review examines the existing literature on the medicinal uses, phytochemistry and biological activities of E. obtusifolia. This study revealed that the bark, branch, fruit, leaf, root, stem, stem bark and twig decoction or infusion of E. obtusifolia are mainly used to treat and manage sore throat, retained placenta in both humans and animals, teething pain, toothache, abdominal pains, menstrual problems and pain. Phytochemical research revealed that the species is characterized by alkaloids, flavonoids, glycosides, phenolics, phlobatannin, saponin, steroids, tannins and terpenoids. Ethnopharmacological research revealed that the extracts and phytochemical compounds isolated from the species showed antibacterial, anti-diarrhoeal, anti-inflammatory, antinociceptive, antioxidant, cytotoxicity and phytotoxicity activities. Ehretia obtusifolia should be subjected to detailed phytochemical, biological and toxicological studies.

Keywords

Boraginaceae, Ehretia obtusifolia, Ehretiaceae, ethnopharmacology, indigenous pharmacopoeia, medicinal plants, pharmacological properties, phytochemistry, traditional knowledge

Introduction

The genus Ehretia P.Br. is a genus of approximately 40 species belonging to the Ehretiaceae family (Gottschling et al., 2016). Recent molecular and phylogenetic studies based on nuclear (ITS) and plastid loci (rps16, trnL-trnF and trnS-trnG) supported the segregation of the family Ehretiaceae from Boraginaceae sensu lato (Gottschling, Diane, Hilger, & Weigend, 2004; Gottschling, Luebert, Hilger, & Miller, 2014). The plant species belonging to the genus Ehretia have been recorded in the Old and New World tropics with centres of diversity in tropical Africa and East Asia (Hilger & Gottschling, 2002). Ehretia obtusifolia Hochst. ex DC. (Figure 1) naturally in Afghanistan, Angola, Botswana, Chad, Eritrea, Ethiopia, Eswatini, Gulf States, India, Iran, Kenya, Madagascar, Malawi, Mozambique, Myanmar, Namibia, Oman, Pakistan, Saudi Arabia, Socotra, Somalia, South Africa, South Sudan, Tanzania, Uganda, Yemen, Zambia and Zimbabwe (Martins, Brummitt, Boraginaceae, Launert, & Pope, 1990; Riedl, 1967; Riedl, Meijer, Huang, Richard, & Barlow, 1997).

The genus name Ehretia is in honour of a German botanical artist and entomologist of the 18th century known as Georg Dionysius Ehret (1708-1770) (Palmer & Pitman, 1972). The species name obtusifolia means obtuse leaves (Glen, 2004), that is, blunt-leaved in Latin in reference to the often blunt leaf tips of the species as shown in Figure 1. Synonyms of E. obtusifolia include E. braunii Vatke, E. caerulea Gürke, E. coerulea var. glandulosa Suess., E. fischeri Gürke, E. laevis (Rottler ex G.Don) Roxb. var. aspera C.B. Clarke, E. mossambicensis Klotzsch and E. obovata R.Br. (Germishuizen & Meyer, 2003; Retief & Wyk, 2001). The English common names of E. obtusifolia include “hairy puzzle-bush” and “stamperwood” (Palgrave, 2002).

Ehretia obtusifolia (Figure 1) is a deciduous, multi-stemmed shrub or small tree growing to a height of five metres (Palgrave, 2002). The species has been recorded at medium to low altitudes on sandy loam to stony soil on hill slopes and termite mounds in grassland, bushland, thickets and woodland. The bark of the species is whitish, light brown, light grey to dark grey, smooth and occasionally flaky. The leaves of E. obtusifolia are alternate or clustered on short lateral shoots, simple, obovate to oblanceolate in shape, dark green above and paler green below with dense and glandular hairs on the midrib and side veins. The flowers are small, blue and mauve in colour (Figure 1) and sweetly scented.

The fruits of E. obtusifolia are spherical in shape, fleshy with glandular hairs, orange in colour and often produced in profusion. The fruits of E. obtusifolia are eaten particularly by children (Jabeen, Khan, Ahmad, Zafar, & Ahmad, 2009; Schmidt, Lotter, & Mccleland, 2007). The leaves of E. obtusifolia are used as fodder in Pakistan (Al-Sodany, Bazaid, & Mosallam, 2013; Sher, Khan, & Hussain, 2011) and Saudi Arabia (Ajaib, Ashraf, Riaz, & Siddiqui, 2014; Iqbal & Hamayun, 2004). It is therefore, within this context that the current study was undertaken aimed at documenting the ecological, biological and medicinal properties of E. obtusifolia in tropical Africa and Asia.

Materials and Methods

Results of the current study are based on a literature search on the ecological, biological and medicinal properties of E. obtusifolia throughout its distributional range using information from internet databases. The databases used included Scopus, Google Scholar, PubMed and Science Direct. Other sources of information used included pre-electronic sources such as journal articles, theses, books, book chapters and other scientific articles obtained from the university library.

Results and Discussion

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Figure 1: Ehretia obtusifolia A:branch showing leaves, flowers and fruits, and B: branch showing flower and fruits (photos: B Wursten)

Table 1: Medicinal uses of Ehretia obtusifolia

Medicinal uses

Parts used

Country

References

Abdominal pains

Root decoction taken orally

South Africa, Tanzania and Zimbabwe

(Gelfand, Mavi, Drummond, & Ndemera, 1985; Watt & Breyer-Brandwijk, 1962)

Diarrhoea

Root infusion taken orally

South Africa

(Hutchings, Scott, Lewis, & Cunningham, 1996; Watt et al., 1962)

Eye problems

Root decoction applied topically

Tanzania

(Nahashon, 2013)

Fungal infections

Stem bark decoction applied topically

Somalia

(Hedberg et al., 1982; Hutchings et al., 1996)

Gonorrhoea

Root decoction taken orally

East Africa

(Hutchings et al., 1996; Kokwaro, 2009)

Infertility in women

Root infusion taken orally

Zimbabwe

(Gelfand et al., 1985)

Malaria

Branch and stem decoction taken orally

Pakistan

(Shah & Rahim, 2017)

Menstrual problems

Bark, fruit and root infusion taken orally

East Africa, Pakistan and Zimbabwe

(Schmelzer et al., 2008; Shah et al., 2013)

Pain

Root, stem and twig decoction taken orally

Botswana, South Africa, Tanzania and Zimbabwe

(Hedberg et al., 1982; Wentzel & Ginkel, 2012)

Retained placenta in humans and animals

Root decoction taken orally

Pakistan and Zimbabwe

(Gelfand et al., 1985; Shah et al., 2013)

Skin diseases

Stem bark applied topically

Somalia

(Hedberg et al., 1982; Hutchings et al., 1996)

Sore throat

Leaf infusion taken orally

Pakistan and Zimbabwe

(Gelfand et al., 1985; Shah et al., 2013)

Spleen problems

Root infusion taken orally

East Africa

(Kokwaro, 2009)

Teething pains in infants and toothache

Leaf decoction taken orally

Pakistan and Zimbabwe

(Gelfand et al., 1985; Shah et al., 2013)

Venereal diseases

Root decoction taken orally

Pakistan

(Shah et al., 2017)

Wounds

Leaf decoction applied topically

Kenya

(Hutchings et al., 1996; Kokwaro, 2009)

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Figure 2: Main diseases and ailments treated and managed by Ehretia obtusifolia in tropical Africa and Asia

Medicinal uses of Ehretia obtusifolia

The herbal concoctions prepared from the bark, branch, fruit, leaf, root, stem, stem bark and twig decoction or infusion of E. obtusifolia are used to treat and manage 17 human and animal diseases and ailments in tropical Africa and Asia (Table 1). The major diseases and ailments treated by E. obtusifolia extracts include retained placenta in both humans and animals, sore throat, and teething pain and toothache recorded in two countries based on three literature records (Figure 2), followed by abdominal pains (three countries, four literature records), menstrual problems (three countries, five literature records) and pain (four countries, six literature records). Other diseases recorded in a single country but based on at least two literature records include diarrhoea, fungal infections, gonorrhoea, skin diseases and wounds (Table 1).

Phytochemical and nutritional composition of Ehretia obtusifolia

Researchers identified phytochemical and nutritional elements from the fruits, leaves, stem bark and whole plant parts of and leaves of E. obtusifolia (Table 2). The phytochemical compounds identified from the species include alkaloids, flavonoids, glycosides, phenolics, phlobatannin, saponin, steroids, tannins and terpenoids (Huma et al., 2018; Huma, 2014; Iqbal et al., 2005).

Biological activities of Ehretia obtusifolia

The following biological activities have been documented from the leaf, fruit and stem bark of E. obtusifolia as well as phenolic compounds isolated from the species: antibacterial, anti-diarrhoeal, anti-inflammatory, antinociceptive, antioxidant, cytotoxicity and phytotoxicity activities.

Antibacterial activities

(Huma, 2014) evaluated the antibacterial activities of the methanolic extracts of leaf, fruit, stem bark of E. obtusifolia against Staphylococcus aureus, Clavibacter michiganensis, Proteus vulgaris and Xanthomonas perforans using disc-agar diffusion with streptomycin (0.05 mg/kg) as the positive control. The extracts exhibited weak activities with a zone of inhibition ranging from 2.0 mm to 7.0 mm in comparison to the zone of inhibition of 26.2 mm to 32.1 mm exhibited by the positive control (Huma, 2014).

Anti-diarrhoeal activities

(Huma, 2014) evaluated the anti-diarrhoeal activities of the methanolic extracts of leaf, fruit, stem bark of E. obtusifolia using the gastrointestinal motility model with atropine as a positive control. The extracts showed activities with anti-diarrhoeal effects ranging from 56.9% to 79.2% in comparison to 86.0% exhibited by the positive control (Huma, 2014).

Table 2: Phytochemical and nutritional composition of Ehretia obtusifolia

Chemical and nutritional components

Value

Plant part

Reference

Nutritional component

Amino acids

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Ash (%)

3.0 – 8.0

Fruits, leaves and stem bark

(Huma, 2014)

Cadmium (ppm)

0.002 – 0.01

Fruits, leaves and stem bark

(Huma, 2014)

Carbohydrates (%)

40.2 – 41.1

Fruits, leaves and stem bark

(Huma, 2014)

Chromium (ppm)

0.08 – 0.1

Fruits, leaves and stem bark

(Huma, 2014)

Cobalt (ppm)

0.001

Fruits, leaves and stem bark

(Huma, 2014)

Copper (ppm)

0.1 – 0.2

Fruits, leaves and stem bark

(Huma, 2014)

Crude fibre (%)

9.7 – 20.9

Fruits, leaves and stem bark

(Huma, 2014)

Fats (%)

6.8 – 8.8

Fruits, leaves and stem bark

(Huma et al., 2018; Huma, 2014)

Iron (ppm)

1.6 – 6.5

Fruits, leaves and stem bark

(Huma, 2014)

Lead (ppm)

0.001 – 0.2

Fruits, leaves and stem bark

(Huma, 2014)

Magnesium (ppm)

43.7 – 280.0

Fruits, leaves and stem bark

(Huma, 2014)

Manganese (ppm)

0.1 – 0.4

Fruits, leaves and stem bark

(Huma, 2014)

Moisture (%)

17.7 – 26.3

Fruits, leaves and stem bark

(Huma, 2014)

Nickel (ppm)

0.1 – 0.2

Fruits, leaves and stem bark

(Huma, 2014)

Protein (%)

7.0 – 11.4

Fruits, leaves and stem bark

(Huma et al., 2018; Huma, 2014)

Reducing sugar

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Sodium (ppm)

5.0 – 5.3

Fruits, leaves and stem bark

(Huma, 2014)

Starch

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Zinc (ppm)

0.2 – 0.4

Fruits, leaves and stem bark

(Huma, 2014)

Chemical component

Alkaloids

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Caffeic anhydride

Whole plant

(Iqbal et al., 2005)

Flavonoids (mg/g)

24.4 – 34.1

Leaves, fruits and stem bark

(Huma et al., 2018)

Glycosides

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Methyl 2-O-feruloyl-1a-O-vanillactate

Whole plant

(Iqbal et al., 2005)

Methyl rosmarinate

Whole plant

(Iqbal et al., 2005)

Phenolic content (mg/g)

34.1 – 38.0

Leaves, fruits and stem bark

(Huma et al., 2018)

Phlobatannin

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Rosmarinic acid

Whole plant

(Iqbal et al., 2005)

Saponin

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Steroids

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Tannins

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Terpenoids

Leaves, fruits and stem bark

(Huma et al., 2018; Huma, 2014)

Trans 4-hydroxycyclohexyl-2-O-p-coumaroyl β-ᴅ-glucopyranoside

Whole plant

(Iqbal et al., 2005)

Anti-inflammatory activities

Iqbal et al. (2005) evaluated the anti-inflammatory activities of the phenolic compounds methyl 2-O-feruloyl-1a-O-vanillactate, caffeic anhydride, trans 4-hydroxycyclohexyl-2-O-p-coumaroyl β-ᴅ-glucopyranoside, methyl rosmarinate, rosmarinic acid isolated from whole plant parts of E. obtusifolia using the in vitro lipoxygenase inhibition assay with baicalein as the positive control. All the compounds exhibited activities with half maximal inhibitory concentration (IC50) values ranging from 0.3 µM to 55.7 µM in comparison to IC50 value of 22.7 µM exhibited by the positive control (Iqbal et al., 2005). (Huma, 2014) evaluated the anti-inflammatory activities of the methanolic extracts of leaf, fruit, stem bark of E. obtusifolia at three different dose levels of 100.0 mg/kg, 200.0 mg/kg and 300.0 mg/kg using the carrageenan-induced mice paw edema method with diclofenac sodium as the positive control. The extracts exhibited dose and time dependent activities, which were comparable to activities exhibited by the positive control (Huma, 2014).

Antinociceptive activities

(Huma, 2014; Huma, Ibrar, Hadi, Barkatullah, & Gigyani, 2018) evaluated the antinociceptive activities of methanolic extracts of leaves, fruits and stem bark of E. obtusifolia in Albino mice using the hot plate assay with diclofenac sodium as a positive control. The responses of latency of the tested mice were noted in a hot plate for the total duration of three hours with 30 minute intervals after each treatment. The extracts exhibited dose dependent activities by showing analgesic effects in mice by reducing duration and intensity of pain in all assessment times (Huma, 2014; Huma et al., 2018).

Antioxidant activities

(Huma et al., 2018; Huma, 2014) evaluated the antioxidant activities of methanolic extracts of leaves, fruits and stem bark of E. obtusifolia using the 1,1-diphenyl-2-picryl hydrazyl (DPPH) free radical scavenging assay with ascorbic acid as a positive control. The extracts exhibited activities with the best inhibition activity of 98.6% and IC50 value of 0.03 µg/ml (Huma et al., 2018; Huma, 2014).

Cytotoxicity activities

(Huma, 2014) evaluated the cytotoxicity activities of the methanolic extracts of leaf, fruit, stem bark of E. obtusifolia using the brine shrimp (Artemia salina) cytotoxicity assay with tamoxifen as the positive control. The extracts exhibited activities with median lethal dose (LD50) values ranging from 16.1 µg/mL to 180.0 µg/mL, which was much higher than LD50 value of 6.6 µg/mL exhibited by the positive control (Huma, 2014).

Phytotoxicity activities

(Huma, 2014) evaluated the phytotoxicity activities of the methanolic extracts of leaf, fruit, stem bark of E. obtusifolia using the Lemna minor phytotoxic bioassay with atrazine as the positive control. The fruit extract exhibited moderate activities with frond inhibition of 40.0% and FI50 value of 4048.3 µg/mL, which were higher than 87.8% frond inhibition and FI50 value of 8.9 µg/mL exhibited by the positive control (Huma, 2014).

Conclusions

The present review summarizes the ecological, medicinal and biological properties of E. obtusifolia in tropical Africa and Asia. Detailed studies focusing on pharmacological and phytochemical evaluations, including toxicological, in vivo and clinical studies to corroborate the traditional medical applications of the species are recommended.