Evaluation on Composition, Antioxidant and Toxicity of Melaleuca cajuputi Leaves

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Evaluation on composition, antioxidant and toxicity of Melaleuca cajuputi leaves

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Advances in Traditional Medicine ISSN 2662-4052

ADV TRADIT MED (ADTM)

DOI 10.1007/s13596-020-00479-x

Evaluation on composition, antioxidant and toxicity of Melaleuca cajuputi leaves

Arif Azimi Md Noor, Siti Mahirah Yusuf, Wan Nor Amilah Wan Abdul Wahab, Md Faizul Ismal Che Adam &

Mohd Dasuki Sul’ain

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Advances in Traditional Medicine

https://doi.org/10.1007/s13596-020-00479-x RESEARCH ARTICLE

Evaluation on composition, antioxidant and toxicity of Melaleuca cajuputi leaves

Arif Azimi Md Noor¹ · Siti Mahirah Yusuf¹ · Wan Nor Amilah Wan Abdul Wahab¹ · Md Faizul Ismal Che Adam¹ · Mohd Dasuki Sul’ain¹

Received: 9 May 2020 / Accepted: 5 July 2020

Abstract

Melaleuca cajuputi (MC) is an aromatic herb that belongs to Myrtaceae family. MC leaves are widely used as traditional medicine, cooking flavour and freshening agent in cosmetics. In this study, the proximate analysis of MC leaves comprised of moisture (2.74%), ash (7.76 ± 0.04%), crude fat (4.83 ± 0.20%), calorie (4974 Cal/g), dietary fibre (9.49 ± 0.01%), protein (6.42 ± 0.06%) and carbohydrates (78.25 ± 1.02%). Besides that, in BSLA only MCME produced toxicity effect with LC₅₀ value of 427 µg/mL while MCEO, MCAE and MCDE not showed any toxicity effect based on Meyer’s and Clarkson’s classification. Moreover, MCME produced the highest TPC and TFC value followed with MCAE, MCEO and MCDE which indicated highest free radical scavenging activity. Next, GCMS analysis revealed that 19 compounds are found in MCEO that possess antidepressant and anxiolytic effects. Furthermore, the concentrations of heavy metals in MCEO (lead, cadmium, arsenic and mercury) are within normal range concentrations based on British pharmacopoeia 2008.

Keywords Melaleuca cajuputi · Myrtaceae · Heavy metals · Meyer’s and clarkson’s classification

Introduction

The used of plants as source of food and medicine already been practiced for over centuries as people during that time mostly rely on flora and fauna (Idris et al. 2019). The usage of herbal medicine in china and Ayurvedic medicine already being acknowledge to be practised for more than 5000 years (Idris et al. 2019). Today, plants are widely used as sources of medicine in other part of countries to produce various of high efficacy and qualities of drugs (Ezhilan and Neela- megam 2012). Among medical plant that has been used for ages in traditional medicine is Melaleuca cajuputi (MC) or locally known as gelam that can be found surrounding humid and hot climate zone of Australia, Thailand, Myanmar and Asian mainland (Daud et al. 2015; Sakasegawa et al.

2003). MC is a fast-growing tree and grows at riverbanks, inlands, sub-coastal and coastal region (Daud et al. 2015;

Sakasegawa et al. 2003). MC leaves are arranged alternately, lanceolate shape and dark green colour (Daud et al. 2015).

Moreover, the flowers are produced in cluster across the stem and their fruit contains abundant of tiny seeds (Sakasegawa et al. 2003).

Apart from that, the young leaves of MC can be eaten as vegetables and as traditional medicine to treat influenza, cough, internal disorder, stomach cramps and intestinal problems (Daud et al. 2015). The leaves can be consumed freshly or cooked and might contains certain nutritional components. Previous study reported medicinal plants are rich with iron, protein, calories, flavour and therapeutic value that used in diets to prevent nutrient insufficiency and degenerative disorders. But several of local vegetable materials are not fully utilized due to insufficient scientific knowledge of nutritional values.

Besides that, MC also possess essential oil (EO) that can be extracted from several parts of herbaceous sources such as leaves, flowers, twigs, buds, bark, roots and seeds which used in traditional medicine (Hashemi et al. 2020). The essential term meaning that a pleasant essences that originated from plant source that have various of chemical combinations such as terpenes and non-terpenes compounds as their major constituents (Kumari et al. 2014). EO are complex mixers that contained various of single compounds that able to exert either therapeutic or adverse effects (Prabuseenivasan et al. 2006).

* Arif Azimi Md Noor [email protected]

1 School of Health Science, Universiti Sains Malaysia Health Campus, 16150 Kubang Kerian, Kelantan, Malaysia

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A. A. M. Noor et al.

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Moreover, EO obtained from medicinal plants and herbs have been reported to be non-toxic and non-persistent to human being with some exceptions (Roszaini et al. 2013).

Although various types of plant already showed good therapeutic activities but some of them still possessed toxicity properties. The toxicity of the plant may originate from the compounds itself or contaminants (Hamidi et al. 2014).

Brine shrimp lethality assay (BSLA) are used to screen toxicity in plant extracts, metal ions, heavy metal, dental materials, cyanobacteria, marine natural products and nano- particles (Hamidi et al. 2014).

Besides that, atomic absorption flame emission spectro- photometer is used to detect heavy metal and those that have density for more than 4 g/cm³ are called heavy metals (Abu- Darwish et al. 2011; Nagajyoti et al. 2010). Accumulation of heavy metal like lead, cadmium, arsenic and mercury in soil able to cause adverse effect to soil organism, crop growth and food safety as roots are primary contact site to the such metal (Nagajyoti et al. 2010). But some of heavy metals are functioning as essential micronutrient to animal and plant such as copper and zinc, but it still caused toxicity effect if consumed in excess (Nagajyoti et al. 2010).

Apart from that, generally plant contained secondary metabolites such as flavonoids and phenolic compound which are natural source of antioxidants (Kamtekar et al.

2014). A good antioxidant should be readily absorbed, reduced free radicals, chelate redox metals and work in membrane and aqueous domains, together with gene expres- sion in positive way (Safaa et al. 2010). Moreover, certain antioxidants able to interact with other antioxidants to regen- erate their original properties (Safaa et al. 2010). Therefore, the objectives of this study are to evaluate proximate analysis of MC leaves together with toxicological and antioxidant properties of four different types of leaves extracts which are MC aqueous extract (MCAE), MC decoction extract (MCDE), MC methanol extract (MCME) and MC essential oil (MCEO). In this study only MC decoction extract (MCDE) and MC essential oil (MCEO) showed the lowest toxicity effect according to Meyer’s and Clarkson’s classification. Moreover, we chose to conducted preliminary study on MCEO regarding antidepressant and anxiolytic properties because it showed better free radical scavenging activity in TPC and TFC results compared to MCDE. The antidepressant and anxiolytic properties are assessed by phytochemicals and heavy metals contents.

Materials and methods

Preparation of four types of MC leaves extract MC leaves are collected from Kampung Gong Kulim in dis- trict of Pasir Puteh, Kelantan Malaysia. MCEO is extracted

from the leaves via steam distillation method. The distillation process produced 18% yields of cajuput essential oil. Certificate of the species authentication obtained from UIAM and UKM Botany experts, PIIUM 0304. Besides that, for MCAE and MCDE, the leaves are prepared by soaking the leaves into the distilled water for 10 min, but MCDE is in heated condition while for MCME, the leaves are soaked in methanol for a few minutes. All of the extracts collected in scope bottle.

Proximate analysis

MC leaves samples are dried and blended to powder form.

The moisture, ashes, crude fibre, crude fat, dietary fibre, total carbohydrate contents and protein are determined according to association of official analytical chemists AOCS, 1999 (Abdu et al. 2015; Akubugwo et al. 2007).

Brine shrimp lethality assay (BSLA)

Cytotoxic activity LC₅₀, of MCAE, MCDE, MCEO and MCME are determined according to previous study (Achakzai et al. 2019).

Total phenolic content (TPC) and Total flavonoid content (TFC)

TPC and TFC value of MCAE, MCAE, MCEO and MCME are measured and calculated via Folin-ciocalteu and alumin- ium chloride colorimetric method (Baba and Malik 2015).

Gas chromatography–mass spectrometry (GCMS) The chemical compositions of MCEO are analysed by using gas chromatography (Shimadzu GC-17A) that is connected to a mass spectrometry (Shimadzu QC-5000 MSD) as described by previous study (Tajidin et al. 2012).

Heavy metal analysis

The composition of lead, cadmium, arsenic and mercury in MCEO are determined by flame atomic absorption spectro- photometer as previously described by previous study (Abu- Darwish et al. 2011).

Statistical analysis

All data are presented as mean ± SD. Statistical significance at the 95% probability levels are set at p < 0.05. Graph pad prism version 7 is used for statistical analysis.

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Evaluation on composition, antioxidant and toxicity of Melaleuca cajuputi leaves

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Results

Discussion

The proximate analysis is only subjected to dry matter, so MC leaves (powder form) are used and not the MC leaves extracts (Abdu et al. 2015; Akubugwo et al. 2007). Table 1, showed low moisture content in MC leaves which are 2.74% which can be considered as good, because water content in vegetable drugs should not be more than 14% deterioration (Abdu et al. 2015). High moisture content able to induce degradation activity that caused by oxidation, enzymes, hydrolysis process and microorganisms development which are the main factors that caused herbal and drugs formulations deteriorated (Abdu et al. 2015). Ash content represents both physiological ash that derived from plant tissues due to biochemical processes and non-physiological ash that comprised of extraneous matter residue (Abdu et al. 2015). Both of them are purposely or non-purposely attach to the plant samples. The ash content comprise of phosphates, chlorides, carbonates, nitrates, various metals silicates and sulphates that formed from the environment or soil (Abdu et al. 2015). The ash content is below the European Pharmacopoeia maximum acceptable limit of 14% that indicated low contamination, adulteration or substitution by minerals (Vaikosen and Alade 2011). Next, crude fat content of MC leaves is 4.83% which is higher when compare to the leaves of sweet potato (0.38–1.91%) and leaves of moringa (2.23%). So MC leaves, should be more appetizing compared to sweet potato leaves because dietary fats able to increase food tastiness by retained and absorbed the flavours (Owusu et al. 2008). Diet that provided one to 2% of its caloric energy as fat is considered as sufficient to human because high fat consumption able to cause cardiovascular disorders like atherosclerosis (Owusu et al. 2008).

Moreover, high calorie content of MC leaves which is 4974 Cal/g can be used for formulation of several dietary sup- plements. The calorie content is the highest when comparing with other herbs like Moringa oleifera leaves (3397 Cal/g), C. sinensis (674.2 Cal/g), P. perfoliatum (573.8 Cal/g) and L.

javanica (506.4 Cal/g) (Narzary et al. 2015; Yaméogo et al.

2011). Next, for crude fibre content, the average result showed 36.3% which is higher compared to Moringa leaves (19.25%) and water spinach (17.67%) while total dietary fibre result is 9.49%. So, high fibre content able to prevent colon cancer, aid in digestion, increase serum cholesterol, excrement moisture content and bile acid excretion (Owusu et al. 2008;

Umar et al. 2007). But, high fibre content also can caused low nutrient bioavailability and intestinal irritation (Umar et al.

2007). The richest sources of dietary fibre usually came from non -starchy vegetables that usually consumed for treatment of gastrointestinal disorders, diabetes and obesity (Owusu et al. 2008). Besides that, the protein content is 6.42%, which is more lower compared to A. hydridus leaves (17.92%) and Lesianthera africana (14.9%) (Akubugwo et al. 2007). Previ- ous study stated that, good source of protein is a plant food, that produced more than 12% of its calorific value from (Aku- bugwo et al. 2007). Moreover, bioavailability of proteins and minerals can be inhibited with tannins presence (Akubugwo et al. 2007). Furthermore, total carbohydrate content is 78.25%

which indicated high energy content in the MC leaves and available carbohydrate content is 87.74%, meaning that it is highly digested and absorbed by the small intestine.

Next, the brim shrimp test is used to predict cytotoxicity activity of MCAE, MCDE and MCME. The LC₅₀ value (µg/

mL) for MCAE, MCDE and MCME are 1062, 2477 and 427.

According to Meyer’s toxicity index the extract is considered as toxic when LC₅₀ less than 1000 µg/mL while when LC₅₀ more than 1000 µg/mL it is considered as not toxic (Hamidi et al. 2014). Besides that, Clarkson’s classify toxicity as LC₅₀ more than 1000 µg/mL (not toxic), 500–1000 µg/mL (low toxicity), 100–500 µg/mL (moderately toxic) and 0–100 µg/

mL (very toxic) (Hamidi et al. 2014). So based on Table 2, MCEO, MCAE and MCDE are considered as non-toxic while MCME is considered as toxic according to both Meyer’s and Clarkson’s toxicity classification. Based on this result, MCEO, MCAE and MCDE that are usually used in traditional medicine preparation are found to be safe, suitable to be used as treatment and pose no acute toxicity threat. Moreover, previous study stated that LD₅₀ for MCAE in mice and rats were 2–5 g/

kg and 3870 mg/kg when administered orally (Russell 1999).

But, in other study LD₅₀ in mice and rats were 540 mg/kg and 850–1560 mg/kg due to high contents of methyleugenol (99%) (Abdo et al. 2001). The toxicity effect of MCME might due to alcoholic solvent that able to rupture cell membranes and extracted greater amount of endocellular materials compared to other extracts (Arslanyolu and Erdemgİl 2006). Although MCME is found to be toxic, it still can be used for development of pesticides, insect repellent or poison for hunting purposed. But, previous toxicity study reported that MCME not showed any toxicity effects on male and female Sprague Dawley rats reproductive system (Daud et al. 2018). Thus, certain factors like clearance rate, substance capacity to pen- etrate the tissue and product excretion, cannot be implemented

Table 1 Results of proximate analysis of MC leaves samples, the results are expressed as mean ± SD, p < 0.05

Moisture (%) Ash (%) Crude fat (%) Calorie (Cal/g) Crude fibre (%) Dietary fibre (%) Protein (%) Carbohydrates (%) 2.74 ± 0.30 7.76 ± 0.04 4.83 ± 0.20% 4974 36.3 ± 3.00 9.49 ± 0.01 6.42 ± 0.06% 78.25 ± 1.02%

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when using cellular model should be considered. Besides that, in vivo metabolism may cause some substances that less toxicity become more toxicity metabolite when exposed to liver enzyme and vice versa (Mensah et al. 2019). Moreover, changes rate of extracts and exposure time are not same both in vitro and in vivo studies. Furthermore, further study regarding acute and chronic toxicity effects should be conducted in vivo to gather more fruitful result.

Besides that, phenolics are considered as largest group of phytochemicals while flavonoids are the largest group of phenolic compounds that are produced natu- rally. The TPC values is categorized into 3 groups, high (TPC > 400 mg GAE/g), moderate (150–400 mg GAE/g) and low (TPC < 150 mg GAE/g) (Safaa et al. 2010). Based on Table 3 result, all of the MC leaves extracts belongs to low level TPC, which yield low free radical scavenging activity. But, among all of the extracts, MCME showed the highest TPC (mg GAE/g) and TFC (mg QE/g) values, probably due organic solvent tend to extract more bioactive constituents due to their ability to destroy the cell wall to extract more endocellular materials and acidic properties followed by MCAE, MCEO and MCDE (Azizah et al. 2014; Ismaila et al. 2012; Mensah et al. 2019). This study also showed that free radical scavenging activities are gradually decreased starting from MCME followed by MCAE, MCEO and MCDE. Previous study stated that,

the phenolics able to suppress oxidative stress by neu- tralizing free radicals (Ismaila et al. 2012). Moreover, the phenolic compounds also able to prevent various type of oxidizing enzymes and lipids peroxidation, thus protect against cancer and cardiovascular disease (Sulaiman and Balachandran 2012). But further studies regarding antioxidant activities of all extracts should be assessed with DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP) assay, β-carotene bleaching assay and metal chelating assay.

Next, because MCEO showed the best toxicity and free radical scavenging activity it is chose to assess antidepressant and anxiolytic properties by determined the phytochemicals and heavy metals contents. In this study, GCMS result showing about 65 compounds have been identified in MCEO that analysed by using gas chromatography–mass spectrometry (GCMS) but only 19 compounds are found to possess antidepressant and anxiolytic effect as shown in Table 4. Previous study reported that, most of dominant compounds in MCEO are terpenoids such as limonene, caryophyllene, cineol, α-terpineol, 4-terpineol and caryophyllene oxide (Białoń et al. 2019; Ukit et al. 2019). This result corresponds with this study which indicates that, the most dominant compounds in MCEO are also terpenoids but slighty differences in terms of compound. Terpenoids are widely used in cosmetics, perfumes, medicines and cleaning products (Khaleel et al. 2018). The differences of bioactive compound might due to plant’s used part, extraction method, ecological conditions, extraction time, geomorphologic, source, season, taxonomic and soil type (Kim et al. 2005; Ko et al. 2009; Kumari et al. 2014). The total percentage of antidepressant compounds that present in MCEO is 41.669% while percentage of anxiolytic compounds is 38.453%.

Lastly, study on heavy metal because previous study reported that exposure of heavy metals is associated with depression and anxiety behaviour in human (Abdellatif et al. 2017; van den Bosch and Meyer-Lindenberg 2019).

Based on Table 5, the concentration of lead (< 0.05 p.p.m), cadmium (< 0.01 p.p.m), arsenic (< 0.01 p.p.m) and mercury (< 0.01 p.p.m) in MCEO are within maximum acceptable concentration and safe to be consumed. Low heavy metal contents in MCEO indicated that the soil and plants are less exposed to agricultural, mines, and waste incinera- tion pollution (Jaishankar et al. 2014). Heavy metals such as lead, cadmium, arsenic and mercury are non-biode- gradable and non-essential heavy metal that are very toxic although at very low concentration because their ability to reabsorb and accumulate divalent metals that lead to organ toxicity (Barbier et al. 2005). Moreover, they also able to cause oxidative stress that disrupted intrinsic antioxidant defences that lead to cell damage or death.

Table 2 Medial lethal concentration LC₅₀ (µg/mL) of different MC leaves extracts via BSLA

MC extracts LC₅₀ value (µg/

mL)

Classification of toxicity Meyer’s toxicity

index Clarkson’s

toxicity criterion

MCAE 1062 Non-toxic Non-toxic

MCDE 2477 Non-toxic Non-toxic

MCME 427 Toxic Medium toxic

MCEO 2131.1 Non-toxic Non-toxic

Negative control:

10% DMSO and seawater

– Non-toxic Non-toxic

Table 3 Result of TPC and TFC of three different MC leaves extracts, the results are Expressed as mean ± SD, p < 0.05

* (μg GAE/mg) μg of gallic acid equivalent per mg dry weight of plant extract, *(mg QE/g) mg of quercetin equivalents per mg/g of extract weight

Extract TPC (mg GAE/g) TFC (mg QE/g)

MCAE 17.30 ± 0.00 12.30 ± 0.01

MCDE 4.90 ± 0.00 0.14 ± 0.00

MCME 19.29 ± 0.01 13.29 ± 0.05

MCEO 16.53 ± 0.00 11.19 ± 0.02

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Conclusion

For the nutshell, according to the results MC leaves nutrition value can be considered as negligible but it still has health benefits and can be processed as functional foods. To conclude MCEO showed low toxicity effect, possess good free radical scavenging activity, antidepressant and anxiolytic phytochemicals and low heavy metals contents.

Acknowledgements This work was supported by BJIM Grant 1001.

PPSK.AUPSE00113 and authors sincerely thanked PPSK for providing facilities to carry out this project.

Compliance with ethical standards

Ethical statement This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of interest Arif Azimi Md Noor has no conflict of interest. Siti Mahirah Yusuf has no conflict of interest. Wan Nor Amilah Wan Abdul Wahab has no conflict of interest. Md Faizul Ismal Che Adam has no conflict of interest. Mohd Dasuki Sul’ain has no conflict of interest.

References

Abdellatif A, Omar EH, Halima G (2017) The neuronal basis of copper induced modulation of anxiety state in rat. Acta Histochem 119(1):10–17

Abdo KM, Cunningham ML, Snell ML, Herbert RA, Travlos GS, Eldridge SR, Bucher JR (2001) 14-Week toxicity and cell pro- liferation of methyleugenol administered by gavage to F344 rats and B6C3F1 mice. Food Chem Toxicol 39(4):303–316 Abdu BA, Adamu U, Sani SM, Joshua OO (2015) Physical and phy-

tochemicals study of some local herbal remedies. IOSR J Pharm Biol Sci (IOSR-JPBS) 10(4):5–10

Abu-Darwish MS, Al-Fraihat AH, Al-Dalain SYA, Afifi FU, Al-Tab- bal JA (2011) Determination of essential oils and heavy metals accumulation in Salvia officinalis cultivated in three intra-raw spacing in ash-shoubak, Jordan. Int J Agric Biol 13(6):981–985 Achakzai JK, Panezai MA, Kakar MA, Kakar AM, Kakar S, Khan J, Khan NY, Khilji I, Tareen AK (2019) In vitro anticancer MCF- 7, anti-inflammatory, and brine shrimp lethality assay (BSLA) Table 4 Result of phytochemical contents in GCMS analysis that exert antidepressant and anxiolytic effects together with the references in previous study

Time (min) Bioactive compound Percentages (%) Anti- depres- sant

Anxiolytic References

8.1076 α-Pinene 2.026 * * Kong et al. (2017), Yang et al. (2016)

9.5454 β-Pinene 0.338 * * Hritcu et al. (2016)

10.576 α-phellandrene 2.974 * * Lantela et al. (2018), Piccinelli et al. (2015)

10.9195 α-Terpinene 3.556 * Arno et al. (2010)

11.3331 Limonene 1.731 * * Bacanlı et al. (2018), Costa et al. (2013)

11.3904 Eucalyptol 0.697 * * Ceremuga (2017), Garabadu et al. (2015)

12.3828 α-Pinene 20.353 * * Kong et al. (2017), Yang et al. (2016)

13.2608 p-Cymene 0.189 * * Marchese et al. (2017), Tankam and Ito (2014)

13.4962 β-Linalool 0.845 * * Guzmán-Gutiérrez et al. (2012), Harada et al. (2018)

15.6974 4-Terpineol 2.227 * Wang and Heinbockel (2018)

15.8946 p-cymenol 0.153 * * Melo et al. (2011), Melo et al. (2010)

16.0791 4-terpineol 0.744 * Wang and Heinbockel (2018)

19.2728 α-Terpinene 0.117 * * Arno et al. (2010)

19.7945 Eugenol 0.163 * * do Amaral et al. (2013), Garabadu and Krishnamurthy (2014)

20.8482 Methyleugenol 0.038 * * Liu et al. (2019), Norte et al. (2005)

21.3278 β-Caryophyllene 4.943 * * Galdino et al. (2012), Hwang et al. (2019)

22.0657 Humulune 2.112 * Kyrou et al. (2017)

22.4093 Calarene 0.071 * Alam et al. (2015)

24.655 Caryophyllene oxide 0.330 * * González-Trujano et al. (2017)

24.725 Globulol 0.088 * Wang and Heinbockel (2018)

Table 5 Results of heavy metals analysis in MCEO with their maximum limit contents

Parameter Result Maximum limit

Lead < 0.05 Not more than 20.0 p.p.m

Cadmium < 0.01 Not more than 5.0 p.p.m Arsenic < 0.01 Not more than 5.0 p.p.m Mercury < 0.01 Not more than 1.0 p.p.m

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1 3

and GC–MS analysis of whole plant butanol fraction of Rheum ribes (WBFRR). BioMed Res Int 2019:1–8

Akubugwo IE, Obasi NA, Chinyere GC, Ugbogu AE (2007) Nutri- tional and chemical value of Amaranthus hybridus L. leaves from Afikpo, Nigeria. Afr J Biotechnol 6(24):2833–2839 Alam J, Mujahid M, Rahman M, Akhtar J, Khalid M, Jahan Y, Basit

A, Khan A, Shawwal M, Iqbal SS (2015) An insight of pharma- cognostic study and phytopharmacology of Aquilaria agallocha.

J Appl Pharm Sci 5(8):173–181

Arno H, Fischedick JT, Díez ML, Lubbe A, Ruhaak RL (2010) 3.24 chemistry of cannabis. In: Liu H-W, Mander L (eds) Compre- hensive natural products II. Elsevier, Oxford, pp 1033–1084 Arslanyolu M, Erdemgİl FZ (2006) Evaluation of the antibacterial

activity and toxicity of isolated arctiin from the seeds of Centau- rea sclerolepis. Ankara Üniv Eczacılık Fak Derg 35(2):103–109 Azizah O, Mukhtar NJ, Ismail NS, Chang SK (2014) Phenolics, flavonoids content and antioxidant activities of 4 Malaysian herbal plants. Int Food Res J (IFRJ) 21(2):759–766

Baba SA, Malik SA (2015) Determination of total phenolic and flavonoid content, antimicrobial and antioxidant activity of a root extract of Arisaema jacquemontii Blume. J Taibah Univ Sci 9(4):449–454

Bacanlı M, Başaran AA, Başaran N (2018) Chapter 32-effects and usage of a citrus compound, limonene. In: Watson RR, Preedy VR, Zibadi S (eds) Polyphenols: prevention and treatment of human disease, 2nd edn. Academic Press, Cambridge, pp 419–424 Barbier O, Jacquillet G, Tauc M, Cougnon M, Poujeol P (2005) Effect

of heavy metals on, and handling by, the kidney. Nephron Physiol 99(4):105–110

Białoń M, Krzyśko-Łupicka T, Nowakowska-Bogdan E, Wieczorek PP (2019) Chemical composition of two different lavender essential oils and their effect on facial skin microbiota. Molecules 24(18):3270

Ceremuga TE (2017) Investigation of the anxiolytic and antidepressant effects of Eucalyptol (1, 8-Cineole), a compound from Eucalyptus, in the adult male Sprague-dawley Rat. AANA J 85(4):277–284 Costa CARA, Cury TC, Cassettari BO, Takahira RK, Flório JC, Costa

M (2013) Citrus aurantium L. essential oil exhibits anxiolytic- like activity mediated by 5-HT 1A-receptors and reduces cholesterol after repeated oral treatment. BMC Complement Altern Med 13(1):42

Daud D, Gan NNMS, Ali MTM, Tawang A (2015) The effect of Melaleuca cajuputi methanolic leaves extract on body growth, puberty and sperm quality of juvenile male rats. Indian J Bio- technol 11:115–119

Daud D, Alias NLR, Ali MTM, Tawang A (2018) Physical signs of illness, liver functions and reproductive parameters of female rats supplemented with Melaleuca cajuputi methanolic extract. J Appl Pharm Sci 8(04):139–142

do Amaral JF, Silva MIG, de Aquino Neto MR, Moura BA, de Car- valho AMR, Vasconcelos PF, Filho JMB, Gutierrez SJC, Vas- concelos SMM, Macêdo DS (2013) Antidepressant-like effect of bis-eugenol in the mice forced swimming test: evidence for the involvement of the monoaminergic system. Fundam Clin Pharm 27(5):471–482

Ezhilan BPN, Neelamegam R (2012) GC-MS analysis of phytocompo- nents in the ethanol extract of Polygonum chinense leaves. Phar- macogn Res 4(1):11–14

Galdino PM, Nascimento MVM, Florentino IF, Lino RC, Fajemiroye JO, Chaibub BA, de Paula JR, de Lima TCM, Costa EA (2012) The anxiolytic-like effect of an essential oil derived from Spiran- thera odoratissima A. St. Hil. leaves and its major component, β-caryophyllene, in male mice. Prog Neuro-Psychopharmacol Biol Psychiatry 38(2):276–284

Garabadu D, Krishnamurthy S (2014) Diazepam potentiates the anti- diabetic, antistress and anxiolytic activities of metformin in type-2

diabetes mellitus with cooccurring stress in experimental animals.

BioMed Res Int 2014:1–15

Garabadu D, Shah A, Singh S, Krishnamurthy S (2015) Protective effect of eugenol against restraint stress-induced gastrointestinal dysfunction: potential use in irritable bowel syndrome. Pharm Biol 53(7):968–974

González-Trujano ME, Hernández-Sánchez LY, Ocotero VM, Dorazco- González A, Fefer PG, Aguirre-Hernández E (2017) Pharmaco- logical evaluation of the anxiolytic-like effects of Lippia graveo- lens and bioactive compounds. Pharm Biol 55(1):1569–1576 Guzmán-Gutiérrez SL, Gómez-Cansino R, García-Zebadúa JC, Jimé-

nez-Pérez NC, Reyes-Chilpa R (2012) Antidepressant activity of Litsea glaucescens essential oil: identification of β-pinene and linalool as active principles. J Ethnopharmacol 143(2):673–679 Hamidi MR, Jovanova B, Panovska TK (2014) Toxicological evalua-

tion of the plant products using Brine Shrimp (Artemia salina L.) model. Maced Pharm Bull 60(1):9–18

Harada H, Kashiwadani H, Kanmura Y, Kuwaki T (2018) Linalool odor-induced anxiolytic effects in mice. Front Behav Neurosci 12:241

Hashemi M, Hashemi M, Daneshamooz S, Raeisi M, Jannat B, Taheri S, Noori SMA (2020) An overview on antioxidants activity of polysaccharide edible films and coatings contains essential oils and herb extracts in meat and meat products. Adv Anim Vet Sci 8(2):198–207

Hritcu L, Hancianu M, Mihasan M, Cioanca O (2016) Effects of inhaled juniper volatile oil in amyloid beta (1–42)-induced anxiety and depression in laboratory rats. Flavour Fragr J 31(2):149–157 Hwang E-S, Kim H-B, Lee S, Kim M-J, Kim K-J, Han G, Han S-Y,

Lee E-A, Yoon J-H, Kim D-O (2019) Antidepressant-like effects of β-caryophyllene on restraint plus stress-induced depression.

Behav Brain Res 380:112439

Idris OA, Wintola OA, Afolayan AJ (2019) Comparison of the proximate composition, vitamins (ascorbic acid, α-tocopherol and reti- nol), anti-nutrients (phytate and oxalate) and the GC-MS analysis of the essential oil of the root and leaf of Rumex crispus L. Plants 8(3):51

Ismaila S, Iqbal S, Chan KW, Ismail M (2012) Effect of acid and base catalyzed hydrolysis on the yield of phenolics and antioxidant activity of extracts from germinated brown rice (GBR). Molecules (Basel, Switzerland) 17:7584–7594. https ://doi.org/10.3390/molec ules1 70675 84

Jaishankar M, Tseten T, Anbalagan N, Mathew BB, Beeregowda KN (2014) Toxicity, mechanism and health effects of some heavy metals. Interdiscip Toxicol 7(2):60–72

Kamtekar S, Keer V, Patil V (2014) Estimation of phenolic content, flavonoid content, antioxidant and alpha amylase inhibitory activity of marketed polyherbal formulation. J Appl Pharm Sci 4(9):61 Khaleel C, Tabanca N, Buchbauer G (2018) α-Terpineol, a natural

monoterpene: a review of its biological properties. Open Chem 16(1):349–361

Kim JH, Liu KH, Yoon Y, Sornnuwat Y, Kitirattrakarn T, Anantachoke C (2005) Essential leaf oils from Melaleuca cajuputi. Acta Hortic 680:65–72

Ko K, Juntarajumnong W, Chandrapatya A (2009) Repellency, fumi- gant and contact toxicities of Melaleuca cajuputi Powell against Sitophilus zeamais Motschulsky and Tribolium castaneum Herbst.

Thai J Agric Sci 42(1):27–33

Kong Y, Wang T, Wang R, Ma Y, Song S, Liu J, Hu W, Li S (2017) Inhalation of Roman chamomile essential oil attenuates depres- sive-like behaviors in Wistar Kyoto rats. Sci China Life Sci 60(6):647–655

Kumari S, Pundhir S, Priya P, Jeena G, Punetha A, Chawla K, Jafaree ZF, Mondal S, Yadav G (2014) EssOilDB: a database of essential oils reflecting terpene composition and variability in the plant kingdom. Database 2014:1–12

Author's personal copy

(10)

1 3

Kyrou I, Christou A, Panagiotakos D, Stefanaki C, Skenderi K, Kat- sana K, Tsigos C (2017) Effects of a hops (Humulus lupulus L.) dry extract supplement on self-reported depression, anxiety and stress levels in apparently healthy young adults: a randomized, placebo-controlled, double-blind, crossover pilot study. Hormones 16(2):171–180

Lantela DE, Kamal BS, Kamal F (2018) Cannabis and the anxiety of fragmentation—a systems approach for finding an anxiolytic cannabis chemotype. Front Neurosci 12:730

Liu Y-M, Fan H-R, Deng S, Zhu T, Yan Y, Ge W-H, Li W-G, Li F (2019) Methyleugenol potentiates central amygdala GABAergic inhibition and reduces anxiety. J Pharm Exp Ther 368(1):1–10 Marchese A, Arciola CR, Barbieri R, Silva AS, Nabavi SF, Sokeng T,

Jorel A, Izadi M, Jafari NJ, Suntar I (2017) Update on monoter- penes as antimicrobial agents: a particular focus on p-cymene.

Materials 10(8):947

Melo FHC, Moura BA, de Sousa DP, de Vasconcelos SMM, Mac- edo DS, de França Fonteles MM, de Barros Viana GS, de Sousa FCF (2011) Antidepressant-like effect of carvacrol (5-Isopropyl- 2-methylphenol) in mice: involvement of dopaminergic system.

Fundam Clin Pharmacol 25(3):362–367

Melo FHC, Venâncio ET, de Sousa DP, de Franca Fonteles MM, de Vasconcelos SMM, Viana GSB, de Sousa FCF (2010) Anxiolytic- like effect of Carvacrol (5-isopropyl-2-methylphenol) in mice:

involvement with GABAergic transmission. Fundam Clin Phar- macol 24(4):437–443

Mensah MLK, Komlaga G, Forkuo AD, Firempong C, Anning AK, Dickson RA (2019) Toxicity and safety implications of herbal medicines used in Africa. Herb Med 63:1–25

Nagajyoti PC, Lee KD, Sreekanth TVM (2010) Heavy metals, occur- rence and toxicity for plants: a review. Environ Chem Lett 8(3):199–216

Narzary H, Swargiary A, Basumatary S (2015) Proximate and vitamin C analysis of wild edible plants consumed by Bodos of Assam.

India J Mol Pathophysiol 4(4):128–133

Norte MCB, Cosentino RM, Lazarini CA (2005) Effects of methyleugenol administration on behavioral models related to depression and anxiety, in rats. Phytomedicine 12(4):294–298

Owusu D, Ellis WO, Oduro I (2008) Nutritional potential of two leafy vegetables: Moringa oleifera and Ipomoea batatas leaves. Sci Res Essays 3(2):57–60

Piccinelli AC, Santos JA, Konkiewitz EC, Oesterreich SA, Formagio ASN, Croda J, Ziff EB, Kassuya CAL (2015) Antihyperalgesic and antidepressive actions of (R)-(+)-limonene, α-phellandrene, and essential oil from Schinus terebinthifolius fruits in a neuro- pathic pain model. Nutr Neurosci 18(5):217–224

Prabuseenivasan S, Jayakumar M, Ignacimuthu S (2006) In vitro antibacterial activity of some plant essential oils. BMC Complement Altern Med 6:39

Roszaini K, Azah MAN, Mailina J, Zaini S, Faridz ZM (2013) Toxicity and antitermite activity of the essential oils from Cinnamomum

camphora, Cymbopogon nardus, Melaleuca cajuputi and Diptero- carpus sp. against Coptotermes curvignathus. Wood Sci Technol 47(6):1273–1284

Russell M (1999) Toxicology of tea tree oil. Tea Tree 191–201 Safaa Y, Abo-Khatwa AN, Lahwa MAB (2010) Screening of antioxi-

dant activity and phenolic content of selected food items cited in the holly quran. Eur J Biol Sci (EJBS) 2(1):40–51

Sakasegawa M, Hori K, Yatagai M (2003) Composition and antitermite activities of essential oils from Melaleuca species. J Wood Sci 49(2):181–187

Sulaiman CT, Balachandran I (2012) Total phenolics and total flavonoids in selected Indian medicinal plants. Indian J Pharm Sci 74(3):258

Tajidin NE, Ahmad SH, Rosenani AB, Azimah H, Munirah M (2012) Chemical composition and citral content in lemongrass (Cym- bopogon citratus) essential oil at three maturity stages. Afr J Bio- technol 11(11):2685–2693

Tankam JM, Ito M (2014) Sedative, anxiolytic and antidepressant-like effects of inhalation of the essential oil of Ocimum gratissimum L. from Cameroon in mice. J Pharmacogn Phytochem 2(5):1–9 Ukit U, Widiana A, Rahmawati E, Hasby RM (2019) Antibacterial

activities test of Cajuput leaf waste extract (Melaleuca cajuputi Powell) on pathogenic bacteria. J Phys Conf Ser 1402(3):033030 Umar KJ, Hassan LG, Dangoggo SM, Ladan MJ (2007) Nutritional

composition of water spinach (Ipomoea aquatica Forsk.) leaves.

J Appl Sci 7(6):803–809

Vaikosen EN, Alade GO (2011) Evaluation of pharmacognostical parameters and heavy metals in some locally manufactured herbal drugs. J Chem Pharm Res 3(2):88–97

van den Bosch M, Meyer-Lindenberg A (2019) Environmental expo- sures and depression: biological mechanisms and epidemiological evidence. Ann Rev Public Health 40:239–259

Wang Z-J, Heinbockel T (2018) Essential oils and their constituents targeting the gabaergic system and sodium channels as treatment of neurological diseases. Molecules 23(5):1061

Yaméogo CW, Bengaly MD, Savadogo A, Nikiema PA, Traore SA (2011) Determination of chemical composition and nutritional values of Moringa oleifera leaves. Pak J Nutr 10(3):264–268 Yang H, Woo J, Pae AN, Um MY, Cho N-C, Park KD, Yoon M,

Kim J, Lee CJ, Cho S (2016) α-Pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAA-benzodiazepine receptors. Mol Pharmacol 90(5):530–539

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