Open accessReview articleFirst published online 2026-4
Ethnomedicinal Uses,Phytochemistry,Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst. ex Nees) T. Anderson : Systematic Review
This study systematically documented fragmented data on the ethnomedicinal uses, phytochemistry, pharmacological activities and toxicological effects of J. schimperiana (Hochst. ex Nees) T. Anderson in Ethiopia.
Methods
PubMed, Science Direct, Scopus, Google, Google Scholar, and university websites in Ethiopia were searched to retrieve published and unpublished original articles reporting the ethnomedicinal use, phytochemistry, pharmacological activities, and toxicity of J. schimperiana. A total of 273, 25, 13, and 11 studies were included for the ethnomedicinal use, pharmacological activities, phytochemistry, and toxicity reviews, respectively.
Result
The plant was mentioned as a treatment of choice for 47 human ailments. The commonest human ailments, in order of citation, were liver problems, rabies, malaria, sexually transmitted disease, evil eye, anthrax, intestinal parasites, skin problems, wounds, and stomachache. Phytochemical investigations on the different parts of the plant have showed the presence of 23 sary metabolites. The most frequently detected chemicals in the crude extracts and solvent fractions of the plant were Terpenoids, Phenols, Tannins, Steroids, Flavonoids, Saponins, and Alkaloids. The crude extracts and solvent fractions of the plant demonstrated a wide range of pharmacological properties including antimicrobial, bronchodilator, anti-diabetic, antidiarrheal, tracheal relaxant, antitussive, anti-inflammatory, wound healing, hepatoprotective and antioxidant activities. The acute oral toxicity studies revealed generally the plant is safe to use with median lethal oral dose value of greater than 2000 mg/kg dried plant extract in majority of the studies.
Conclusion
J. schimperiana is widely used for the treatment of various human ailments in all regions of Ethiopia. Despite its widespread traditional use, the phytochemical, pharmacological, and toxicological properties of J. schimperiana are not yet fully investigated.
For thousands of years, plants have been employed in traditional medicine. In the majority of underdeveloped nations, using traditional medicine is the normative foundation for maintaining good health. Because they contain multiple active ingredients with significant therapeutic effect, medicinal plants have been a model source for alternative treatments for human problems for millennia.1
The Ethiopian flora is estimated to contain 6500 plant species, of which 12% are endemic. There are roughly 1000 plant species in those Ethiopian floras that have been designated as therapeutic plants.2Justicia schimperiana (Hochst. ex Nees) T. Anderson is one of the medicinal plants the Ethiopian population traditionally relies on. It is a member of the Acanthaceae family, which has around 250 genera and 2500 species. With almost 600 species, Justicia is the biggest genus in the Acanthaceae family.3Adhatoda schimperiana and Gendarussa schimperiana are two other names for the plant. The scientific names of J. schimperiana (Hochst. ex Nees) T. Anderson and its synonym A. schimperiana Hochst. ex Nees and G. schimperiana Hochst. were verified at the International Plant Name Index. It is also known locally as “dhumuugaa” in Afaan Oromo, “Sensel” or “Simiza” in Amharic, and “Surpa,” “Kasha,” or “Keteso” in Sidama.4
J. schimperiana (Hochst. ex Nees) T. Anderson is a typical shrub found in wet highland forests, frequently close to streams and rivers, as well as in evergreen scrub on hill slopes, forest clearings, coffee plantations, unused land, and around homes planted as hedges. It is native to Ethiopia, Eritrea, Tanzania, Somalia, and Kenya. It often grows in altitudes of 1300 and 2800 meters above sea level in the Dry and Moist Weyna Dega and Moist Dega agroclimatic zones in Ilubabor, Kefa, Sidama, Shoa, Addis Ababa, Harerge, Gojjam, Gondar, and Tigray.1
The plant J. schimperiana has numerous medicinal uses in different parts of Ethiopia. Ethnobotanical study reports showed that the plant is used in the treatment of various ailments such as hepatitis, evil eye, jaundice, rabies, asthma, the common cold, stomach-ache, diarrhoea, tapeworm infestation, anthrax, wounds, external parasites, ascariasis, haemorrhoid, headache, and skin irritation.5–13
Its leaves has long been used as remedy for the treatment of abdominal problems in Kembatta,14 skin rash in Cheyla district,15 rabies in Fiche area,16 hepatitis in Nekemte town5, rheumatism in Goma district,17 headache in Wollega Zone18. The root of J. schimperiana is sought for the treatment of gonorrhoea in Cheyla district,15 seizure in Nekemte town,5 evil eye in Libokemkem district,19 liver cirrhosis in Loma and Gena Bosa districts.20
Plants produce a variety of chemicals so called secondary metabolites to defend themselves against invading microorganisms and herbivores. The hexane, ethyl acetate, and chloroform fractionation of the J. schimperiana leaves extract revealed the presence of alkaloids, flavonoids, glycosides, phytosterols, polyphenols, quinines, saponins, and triterpenes.21 Likewise, anthraquinones, flavonoids, glycosides, phenols, saponins, tannins, and terpenoids were detected in the methanolic crude extract of J. schimperiana leaves.22
Medicinal plants that are claimed to be effective by the herbalists need to be confirmed with scientific experiments for their efficacy. The crude extracts of J. schimperiana leaves have been reported to have antibacterial,23,24 antifungal,25 antimalarial26 and antioxidant activities.27
The widespread belief that herbal medications or treatments are extremely safe and free of side effects is not only false but also deceptive. It has been demonstrated that a variety of unfavorable or unpleasant reactions can be produced by herbs, some of which can result in fatal or life-threatening diseases, severe injuries, or even death.28 As a result, it is increasingly customary to investigate the toxic effects of medicinal plants using animal models. A single dose intragastric administration of the ethanol, methanol, and water extracts of J. schimperiana leaves in mice up to a dose of 5000 mg/kg did not reveal any evidence of toxicity.29
Due to its widespread traditional use, J. schimperiana is one of the medicinal plants that attracted researchers’ attention for its ethnomedicinal uses, phytochemistry, pharmacological activities and toxicity. Thus, this review is aimed at systematically pooling fragmented studies carried out on the traditional medicinal uses, chemical constituents, pharmacological activities and toxicological effects of J. schimperiana.
Method
Search Strategy
From September 1, 2025, to October 31, 2025, three authors (MJ, SA and SW) independently searched published and unpublished original research articles that described ethnobotanical information, pharmacological activity, phytochemistry and toxicological effects of J. schimperiana in Ethiopia. An update search was conducted as of November 16, 2025. The databases searched included PubMed, Science Direct, Scopus, Google, and Google Scholar. No date range limitation was in place. The search was limited to research written in English. After the initial search, references in the included publications were thoroughly examined for other researches. The reporting of this systematic review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist30 (Supplementary file 1). The PRISMA flow diagram is shown in Figure 1. The entire search technique, detailing the complete search strategy, databases, full string of keywords, and Boolean operators used, is provided in Supplementary file 2.
PRISMA flow diagram of included studies in the systematic review of the toxicological effect, ethnomedicinal uses, pharmacological activities and phytochemistry of J. schimperiana (Hochst. ex Nees) T. Anderson.
Study Inclusion Criteria
Studies conducted in Ethiopia having pertinent and extractable information on the ethnomedicinal use, phytochemistry, pharmacological activities, and toxicological effects of J. schimperiana were included.
Study Exclusion Criteria
Researches that were not accessible online, regardless of whether they had been published, or that did not reply after two emails were sent to the associated author, were eliminated. Studies that failed to provide our finding of interest were also removed after being examined by three authors (MJ, SA, and SW) in accordance with the procedure described above.
Data Extraction
All the necessary data were collected using a standardized data extraction format in Microsoft Excel by three authors independently (MJ, SA, and BS). Discussions were held among the authors until consensus was reached for any difference in opinion. The data extraction format comprised the following information: author, publication year, ethnomedicinal uses, phytochemical constituents, pharmacological activity, and toxicological effects of J. schimperiana.
Methodological Quality Assessment of Included Studies
Two authors (MJ and SA) independently evaluated the methodological quality of the studies. Checklist for Reporting Ethnobotanical Research (CERES) was used to evaluate the methodological quality of studies reporting the ethno-medicinal activities of J. schimperiana. Additionally, Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias tool was employed for the studies reporting pharmacological activity and toxicity evaluations of J. schimperiana.
Data Analysis
Microsoft Excel 2016 was used to extract the data, which was then exported to Statistical Software Packages for Social Sciences (SPSS) 2631 for additional data cleaning and descriptive analysis. The frequency distributions of study area, ailments treated, plant parts used, route of administration, phytochemical constituents, etc were analysed using SPSS.
Result
Search Result
The search strategy for the Ethnomedicinal uses category yielded a total of 9071 records, with 8810 hits from Google Scholar, 86 records from PubMed, and 175 records from ScienceDirect. The search for Safety, Phytochemistry, and Pharmacological activities resulted in 317 records, comprising 257 results from Google Scholar, 15 results from PubMed, and 45 records from ScienceDirect (Supplementary file 2). From these, a total of 273 primary studies were included for the ethnomedicinal uses while only 28 were included for the safety, pharmacological activity and phytochemistry of J. schimperiana (Figure 1). A single study may report more than one outcome of interest (safety, pharmacological activity and phytochemistry).
Ethnomedicinal Uses of J. schimperiana
A total of 273 ethnobotanical (69 human and 204 both human and livestock) ailment studies were included. In nearly half (49%) of the ethnobotanical studies, J. schimperiana was mentioned as a medicinal plant used to treat at least one human ailment.
As shown in Table 1, nearly 95% of the studies were conducted in the four major regions of Ethiopia (54 in Oromia, 39 in Amhara, 22 in Southern Nations, Nationalities, and Peoples’ Region, and 11 in Tigray). They were conducted in 53 zones and 125 districts in Ethiopia.
Regional Distributions of the Included Studies.
S. No.
Region
Frequency
Percent
1
Oromia
54
40.6
2
Amhara
39
29.3
3
SNNPR
22
16.5
4
Tigray
11
8.3
5
Afar
2
1.5
6
Addis Ababa City Administration
1
0.8
7
Amhara & Benishangul Gumuz
1
0.8
8
Tigray & Afar
1
0.8
9
Somali
1
0.8
10
Benishangul-Gumuz
1
0.8
Total
133
100.0
Key: SNNPR: Southern Nations, Nationalities, and Peoples’ Region.
Human Ailments Treated by J. schimperiana
Related illnesses reported by the primary studies were grouped together in this systematic review. For example, liver problem includes jaundice, “wof beshita”, hepatitis, liver disease, and liver cirrhosis. Majority of the ailments grouped as sexually transmitted disease were gonorrhoea (15 out of 17). Skin problem includes skin rash, lesion, irritation, infection, burn, itching, and eczema. Ailments reported by the primary studies as intestinal parasite, hookworm, tapeworm, ascariasis, and abdominal parasite were grouped together as intestinal parasite. Mental stress, depression, somnambulism, syneresis cerebral, “mefthe seray’, “yeayne bar teza”, “eje seb” were considered as mental disorder.
J. schimperiana was mentioned by traditional healers as a treatment of choice for about 47 different human ailments. Thirty-five of the ailments were mentioned in at least two studies. The most frequently mentioned human ailment was liver problem (42 studies) followed by rabies (38 studies). Malaria and sexually transmitted disease were also among the common human ailments treated by the plant mentioned in 21 and 17 studies, respectively (Supplementary file 3).
Plant Parts Used
Leaf of J. schimperiana is the leading part used to treat human ailments. The leaf has been used to treat about 42 different human ailments alone or mixed with other plant parts. The root alone or mixed with other parts is the second preferred part used as a treatment of human ailments (25 ailments). Root alone was used in about 18 different human ailments. Among the mixed use of J. schimperiana plant parts, a mixture of the root and leaf became the leading combination (14 ailments). Whole plant, shoot, seed, stem, flower, fruit and bark of the plant are rarely used by the traditional healers.
Route of Administration
Variations in the preparation technique and route of administration of J. schimperiana for the same ailment were noticed across studies. Majority of the preparations were administered orally. All forms of external applications, such as washing with water mixed with plant parts, pasting, tying, etc, were considered dermal applications. Fumigating the prepared plant part and inhaling the smoke was considered as nasal administration (Figure 2).
J. schimperiana route of administration.
Phytochemical Screening and Identified Chemical Constituents of Justicia schimperiana
Secondary Metabolite Profile
As shown in Table 2, thirteen studies reported about the phytochemical constituents of J. schimperiana.21–24,27,29,32–38 A test for 23 different secondary metabolites (chemicals) has been done in these thirteen studies (Table 2). The most frequently tested chemicals were Tannins (11 studies), Flavonoids (10 studies), Saponins (10 studies), Terpenoids (8 studies), Alkaloids (6 studies), Steroids (6 studies), Phenols (6 studies), and Glycosides (4 studies). The most frequently detected chemicals were Terpenoids (100%), Phenols (100%), Tannins (92%), Steroids (86%), Flavonoids (83%), Saponins (83%), and Alkaloids (67%). Majority (nine) of the studies tested the leaf extract. One study tested the root, stem and bark and another study tested the leaf and bark. Only one study tested the root extract. The chemical constituents of J. schimperiana showed variations on the type of plant part tested and the solvent used.
Terpenoids were detected in the ethanol leaf extract,36 methanol leaf extract,22,27 ethanol leaf and bark extract,24 chloroform leaf extract,35 methanol and aqueous leaf extract29 of J. schimperiana. J. schimperiana phenols were found in methanol leaf extracts,22,33 methanol and water leaf extracts,35 and methanol and chloroform root extracts.38
Tannins were detected in the ethanol leaf extract,36 methanol leaf extract,22,27,33 ethanol leaf and bark extract,24 and methanol and chloroform leaf extracts of J. schimperiana. It was also identified in the ethanol29 and methanol29,32 extracts of its leaves. It was also present in the ethyl acetate and aqueous fractionation of the methanol crude leaves extract.32
The ethanol leaf extract,36 methanol leaf extract,27 ethanol leaf and bark extract,24 petroleum root extract,38 and ethanol, hexane, and aqueous leaf, stem bark, and root extracts23 of J. schimperiana all contained steroid like compounds. J. schimperiana flavonoids have been found in ethanolic leaf preparations,36 chloroform leaf extracts,21 methanol leaf extracts,22,33,35 and aqueous leaf extracts.35 Additionally, it was discovered in the plant's ethanol, methanol, hexane, and aqueous leaf, stem bark, and root preparations23 as well as its methanol root extract.38
Saponins were detected in the ethanolic leaf extract,36 chloroform leaf extract,21 methanol leaf extract,22,33 ethanolic leaf and bark extract,24 chloroform, and aqueous leaf extract,35 methanol root extract,38 and ethanol, methanol, hexane, and aqueous leaf, stem bark, and root extracts23 of J. schimperiana.
Among the extracts of J. schimperiana, alkaloids have been found in ethanolic leaf extract,36 chloroform leaf extract,21 ethanolic leaf and bark extract,24 ethanol, chloroform, and aqueous leaf extract,35 and ethanol, methanol, hexane, and aqueous leaf, stem bark, and root extracts23 among others.
Other Compounds Isolated
Fatty Acid Methyl Esters
Twenty-nine different chemicals were discovered in the root extracts of J. schimperiana using GC-MS (Gas chromatography–Mass spectrometry). The most abundant chemicals identified were Methyl tetradecanoate, Methyl hexadecanoate, Methyl elaidate, Methyl palmitoleate, and Methyl Octadecenoate.38
Essential Oils and Volatile Compounds
The essential oil of J. schimperiana leaves yielded twenty-eight chemical components, accounting for 75.18% of the total oil. The major chemical components were eucalyptol (24.13%), espatulenol (7.25%), crypton (5.08%), and 1-octen-3-ol (5.06%).39 In another phytochemical study, the compound ASH-14 was isolated for the first time from leaves extract of J. schimperiana with repeated use of column chromatography.21 More recently, GC-MS analysis of the essential oils from the roots and leaves identified 54 and 52 chemical components, respectively. Furthermore, six compounds-β-sitosterol, 5-methoxy durmillone, trans-resveratrol, tricuspidatol A, kaempferol-3-O-α-rhamnopyranoside, and kaempferol-3-O-rutinoside-were isolated from the root extracts and reported for the first time in this species.34
Pharmacological Activity of J. schimperiana
The pharmacological activity of J. schimperiana was documented in 25 studies. The pharmacological activity studies carried out on J. schimperiana include: antibacterial, antifungal, antimalarial, anti-rabies, bronchodilator, anti-diabetic, tracheal relaxant, antidiarrheal, antitussive, anti-inflammatory, wound healing, hepatoprotective, cytotoxicity, and antioxidant. The specific plant parts, crude extracts, chemical information, and corresponding biological activities from these studies is summarized in Table 3.
Summary of Phytochemical and Pharmacological Investigations of Justicia schimperiana.
Key: -: N/A (Activity Focus); --: N/A (Primary Chemical Screening).
Antibacterial Activities
This systematic review included antibacterial activity reports of J. schimperiana from eight studies.23,24,34,36–39,49 An antibacterial activity study of J. schimperiana essential oil by microdilution method against Escherichia coli and Bacillus subtilis has shown no obvious antibacterial activity.39 Through the use of a disc diffusion assay, petroleum ether, a mixture of methanol and chloroform (1:1), and methanol crude root extracts demonstrated growth inhibition against two Gram-positive (Staphylococcus aureus and streptococcus pyogenes) and two Gram-negative (E. coli and Salmonella typhi) bacteria.38
E. coli, S. aureus, Campylobacter jejuni, and Pseudomonas aeruginosa were significantly inhibited from growing by the ethanol, methanol, and hexane crude extracts of the stem bark of J. schimperiana. The aqueous crude extract, however, did not significantly hamper the growth of E. coli and P. aeruginosa. Antibacterial activities of the ethanol, methanol, hexane and aqueous crude extract of its leaves showed a significant growth inhibition against most tested bacterial strains. Most crude root extracts of the plant showed a significant growth inhibition against some test organisms.23
Antibacterial activities of the extracts against four human bacterial pathogens, E. coli O157: H7 S. Typhi, S. aureus and S. pyogenes were determined using disc diffusion and broth dilution methods. The result of antibacterial activity test showed each extract type had a varying degree of growth inhibition to the four human pathogenic bacterial species, ie, E. coli O157: H7, S. Typhi, S. aureus, and S. pyogenes. Both leaf and bark extracts exhibited the most effective antibacterial activity against S. aureus. Antibacterial activities of both plant extracts were significantly less than that of amoxicillin used as positive control. The antibacterial activity of both leaf and bark extracts showed highest inhibition zones in all concentrations against a Gram-positive bacteria (S. aureus and S. pyogenes) than Gram-negative bacteria (E. coli and S. Typhi).24
The antibacterial activity of the crude extract and solvent fractions was evaluated on eight bacterial (S. aureus, Streptococcus pneumoniae, S. pyogenes, S. typhi, K. pneumoniae, Shigella flexneri, P. aeruginosa and E. coli) species using agar well diffusion method with different concentrations (800, 400 and 200 mg/ml). All solvent fractions demonstrated antibacterial activity and the n-butanol fraction was observed to be more active against the tested microorganisms.37 The ethanolic leaf extract of J. schimperiana showed antibacterial activity against S. aureus, S. typhi and Shigella boydii.36 In addition, essential oil extracts demonstrated significant antibacterial activity, particularly against Staphylococcus aureus and Streptococcus agalactiae. A newly isolated compound, kaempferol-3-O-rutinoside, showed potent antimicrobial activity with a low minimum inhibitory concentration of 0.25 µg/ml.49
Antifungal Activities
Six studies reported on antifungal activity of J. schimperiana.23,25,33,37–39 The antifungal activity of the crude extract and solvent fractions of J. schimperiana was evaluated on two fungal (Candida albicans and Trichophyton mentagrophytes) species using agar well diffusion method with different concentrations (800, 400 and 200 mg/ml). All solvent fractions demonstrated antifungal activity and the n-butanol fraction was observed to be more active against the tested microorganisms.37 The use of J. schimperiana as chewing sticks to manage oral infection caused by C. albicans showed medium antifungal activity and its effect was increased when it was combined with cinnamon.25 Petroleum ether, methanol: chloroform (1:1) mixture and methanol crude root extracts showed growth inhibition against two fungus (Aspergillus niger, Aspergillus flavus) through disc diffusion assay.38
Antifungal activities of the ethanol, methanol, hexane and aqueous crude extract of the stem bark of J. schimperiana showed a significant growth inhibition against all four fungal strains tested (A. niger, A. flavus, C. albicans and Saccharomyces boulardii). All fractions of the crude extract of the leaves of the plant showed a significant growth inhibition against most tested fungal strains. Most crude root extracts of the plant showed a significant growth inhibition against some test organisms.23J. schimperiana has shown no obvious antifungal activity against C. albicans.39 80% methanolic extract of J. schimperiana leaf has shown antifungal activity against C. albicans and A. Vinger.33
Antimalarial Activities
Three studies reported on antimalarial activity of J. schimperiana.26,35,50 The hydroalcoholic extracts of the roots of the plant possess moderate antimalarial activities that prove its traditional claims. The 400 and 600 mg/kg doses of the plant showed significant parasitemia suppression and increased in mean survival time at p ≤ .05.26
The solvent fractions of the leaf of J. schimperiana exhibited a significant chemosuppressive effect, with the methanol and aqueous fractions producing the highest antimalarial activity in the 4-day suppressive test. The methanol fraction also possessed a significant activity in both curative and prophylactic tests in terms of parasitaemia suppression.35
The 80% methanolic crude extract of the leaves of Adhatoda schimperiana dose-dependently reduced parasitaemia induced by chloroquine-sensitive Plasmodium berghei infection in suppressive, curative and prophylactic models in mice. It also improved mean survival time relative to the control and it was comparable to chloroquine, the standard drug.50
Anti-Rabies Virus Activities
Only two studies reported the anti-rabies virus activities of J. schimperiana.29,51 At 5000 mg/kg dose level, the 80% ethanolic crude extracts of the leaves of J. schimperiana (P = .038) significantly increased the survival time of mice.51 Oral treatment of mice infected with rabies virus with ethanol, methanol, and water extracts of the leaves of J. schimperiana at a dose of 3000 mg/kg significantly (p < .05) increased the mean survival time compared to those of negative control group. Similarly, ethanol, methanol, and water extracts of the leaves of the plant showed moderate to good in vitro anti-rabies activity.29
Antidiarrheal Activity
Only one study22 reported antidiarrheal activity. The methanolic leaf extract of J. schimperiana has an antidiarrheal activity as revealed by reductions in the total fecal output and diarrheal drops, intestinal fluid accumulation, and gastrointestinal motility.22
Anti-Diabetic Activity
Three studies assessed the hypoglycemic and antihyperglycemic activity of J. schimperiana.34,52,53 The traditional claim for J. schimperiana's usage in diabetes is supported by its considerable antihyperglycemic activity in streptozotocin-induced diabetic mice, as well as by improvements in glucose tolerance and a small amount of hypoglycemic activity in normal mice. Oral administration of the aqueous extract of the plant (200 mg/kg and 400 mg/kg) showed significant tolerance after one and two hours oral glucose load normoglycemic mice. The extract also produced significant (P < .05) blood glucose reduction at 4 h after its administration in normoglycemic mice. The extract at 400 mg/kg dose level produced significant (P < .05) reduction in blood glucose level at 2, 3 and 4 h of treatment in streptozotocin (45 mg/kg) induced diabetic mice.52 The hydromethanolic root extract also demonstrated antihyperglycemic and antihyperlipidemic effects in Streptozotocin-induced diabetic mice, causing a significant reduction in serum triglycerides, total cholesterol, and low-density cholesterol, while increasing high-density lipoprotein cholesterol.53 Furthermore, in vitro studies revealed that the extracts and isolated compounds possess significant α-amylase inhibitory effects.34,53
Antitussive Activity
Only one study assessed the antitussive activity effect of J. schimperiana.40 In comparison to the negative control group, the crude 80% methanol extract of the plant's leaves significantly lengthened the latent period of coughing (P < .05) and decreased cough frequency (P < .05). The extract's highest antitussive action was seen at a dose of 400 mg/kg/day, which resulted in a 57.5% reduction in cough frequency.40
Bronchodilator Effect
Only two studies reported the bronchodilator activity effects of J. schimperiana.41,47 The plant exhibited anti-inflammatory and bronchodilatory effects on the tracheal chain of the guinea pigs.47 It was found that the chloroform fraction of the crude 80% methanolic extract of the leaves of the plant has a dose-dependent protective role against respiratory distress and tracheal relaxant activity in guinea pigs.41
Tracheal Relaxant Effect
Only one study assessed the tracheal relaxant effect of J. schimperiana.54 The chloroform fraction had a greater tracheal relaxing effect than the raw hydro-alcoholic extract. The intermediate polar column chromatographic elute of the chloroform fraction, which underwent further fractionation, was discovered to have a stronger tracheal relaxing effect than the chloroform fraction.54
Anti-Inflammatory Activities
Only one study assessed the anti-inflammatory activity of J. schimperiana.47 The extract exhibited a moderate degree of anti-inflammatory activity.47
Wound Healing Activity
Only one study assessed the wound healing activity of J. schimperiana.32 The 80% methanol crude extract and solvent (chloroform, ethyl acetate, and aqueous) fractions of J. schimperiana leaves possess wound healing activity.32
Hepatoprotective Activity
Only one study assessed the hepatoprotective activity of J. schimperiana.43 The hydro-alcoholic extracts and methanol fractions of J. schimperiana at a dose of 50 mg/kg possess potent hepatoprotective activity in CCl4 induced liver injury in mice.43
Antioxidant Properties
Four studies reported the antioxidant properties of J. schimperiana.27,34,43,53 The plant has showed significant antioxidant activities expressed with a higher peroxide value.27 The antioxidant activity of J. schimperiana extract was investigated using in vitro DPPH assay. The methanol extracts of the plant possess antioxidant activities and may inhibit the deleterious effect of free radicals generated by CCl4.43 The root extract showed good antioxidant activity in in vitro DPPH assay,53 and further analysis of root essential oils and compounds also revealed strong radical scavenging activity.34
Cytotoxicity
A recent study evaluated the cytotoxicity of J. schimperiana extracts. The essential oil extracts demonstrated moderate cytotoxicity against the Michigan Cancer Foundation-7 cell line (a human breast cancer line).34
Toxicological Effects of J. schimperiana
Eleven acute oral toxicity studies on J. schimperiana in animal models were identified. Two recent studies assessed the effects of sub-acute46 and chronic exposure,42 filling a significant research gap.
Methanol (80%) extract of dried leaves, administered intragastrically to mice, produced median lethal dose (LD50) > 2000 mg/kg. During the 14-day observation of the mice, no deaths or notable toxicity signs were seen.22 Similarly, a limit dose of 2000 mg/kg of an 80% methanolic extract of dried leaves, administered intragastrically to mice, was found to be safe.26 Methanolic extract of the leaves of the plant administered intraperitoneally in mice presented a low toxicity with LD50 value of 1286.76 mg/kg.47 An intragastric administration of its root crude extract to mice produced LD50 > 5000 mg/kg.51
Acute oral toxicity in mice revealed that 80% methanolic extracts of the leaves of the plant does not cause toxicity or mortality at doses up to 1000 mg/kg. However, signs of excitement were noticed in one of the animals at a dose of 1000 mg/kg.43 Acute oral toxicity tests on rats using an aqueous extract of J. schimperiana leaves at a concentration of 2000 mg/kg revealed no evidence of toxicity or mortality, demonstrating the extract's safety.52
Intragastric administration of the water, methanol, and ethanol extracts of the leaves of the plant to mice produced LD50 > 3000 mg/kg. Up to a dose of 3000 mg/kg, mice showed no signs of toxicity; however, at larger doses, such as 4000 and 5000 mg/kg, mice exhibited typical toxicity symptoms like weakness, limited mobility, and hair erection, as well as mortality.29 Oral administration of the chloroform fraction of J. schimperiana leaves demonstrated a higher LD50 value of 5.01 g/kg. Piloerection, stumbling, hypoactivity, and hypnosis were noted at larger doses of the fraction.41
A recent acute toxicity study using the Wistar albino rat model (an appropriate animal model) found that a single oral dose of the 80% methanolic leaf extract resulted in no deaths or serious morbidity, establishing the LD50 as >5000 mg/kg.46 In a sub-acute toxicity study spanning 28 days,46 oral administration of the methanolic leaf extract to Wistar rats was found to be relatively safe. The treatment had no significant effect on general behavior, organ weight, or most biochemical parameters. However, a decrease in hemoglobin and hematocrit was observed in the 1000 mg/kg dose group compared to controls.46
Furthermore, a chronic toxicity study lasting 6 months was conducted on Wistar albino rats.42 Six months of daily oral administration of the plant extract did not significantly affect food consumption, organ weight, or histopathology. However, rats treated with the highest dose 1000 mg/kg showed significantly increased liver enzymes (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphate) and kidney function tests (creatinine and urea). Additionally, this high-dose group showed significantly lower red blood cell count, hemoglobin, and hematocrit compared to the control group, indicating potential adverse effects at high, long-term doses.42
Discussion
This systematic review is aimed at systematically pooling fragmented studies carried out on the traditional medicinal uses, chemical constituents, pharmacological activities and toxicological effects of J. schimperiana. This plant is a very important key component of the traditional medicine of Ethiopia, possessing a practically vast array of biological activities. While the review suggested many traditional applications, most specifically in relation to the treatment of liver and respiratory system related diseases, the issue of a profound imbalance in the extent of traditional use in relation to the level of pharmacological/phytochemical substantiation is clearly outlined.
This systematic review identified widespread documentation of J. schimperiana over 125 districts, and it was mentioned in 49% of the reviewed ethno-botanical studies. This suggests its primary usage as a therapeutic agent in Ethiopian traditional medicine. This consensus over such vast geographical and ethnic divisions, spread over 53 zones, strongly suggests the inherently strong and proven traditional usage of this species.
The findings presented a remarkable number of reports for use in treating liver diseases (42 reports) and for rabies (38 reports). The steady use in treating liver diseases, such as hepatitis and jaundice, can be readily correlated with the phytochemical content of the herb, which includes the presence of phenols and flavonoids, well known for their antioxidant and hepatoprotective effects.55 The use for rabies, on the other hand, can be said to have a complex implication, as it is the second most frequent use, but the herb, based on pharmacological screening, can only show moderate efficacy against rabies. This contradiction in high cultural dependence and modest biological efficacy can, to a certain extent, be explained by the absence of alternative treatment in the region, thus achieving a status as the ‘‘drug of choice’’.
Leaf was identified as the main plant part in use, appearing in the treatment of 42 various ailments. This result is in line with general trends in Ethiopian ethnobotany in that leaves are selected in preference to roots and/or bark.44 This result makes for pleasant conserved afforestation: the use of leaves is much more sustainable than the use of roots, often resulting in the loss of the plant. The regular use of the leaves, especially for oral and dermal formulations, indicates that the active compounds, for example, terpenoids and alkaloids, are present in sufficient concentration in the leaves to exert the desired medicinal property.45 The different preparation methods range from oral decoctions to nasal fumigation and show a high degree of regional understanding regarding the management of different levels of severity.45 This heterogeneity with respect to administration routes indicates that J. schimperiana has a diverse range of biological compounds with varying levels of ability to be absorbed through different physiological routes.
This review identified the most frequently detected chemicals from J. schimperiana to be Terpenoids (100%), Phenols (100%), Tannins (92%), Steroids (86%), Flavonoids (83%), Saponins (83%), and Alkaloids (67%). The presence of a concentrated secondary metabolite of Terpenoids, Phenols, and Tannins strengthens the mechanism of the plant as an anti-inflammatory and antioxidant and attributes to a current hot trend of isolation of these classes of compounds.
This systematic review revealed that J. schimperiana is a source of terpenoids. The high occurrence of terpenoids is important because they are the primary compounds used in the synthesis of steroids, which can also be used as a defense mechanism against diseases. Phenols were abundant in J. schimperiana, as revealed in the review conducted. The high occurrence of the identified phenols in the review provides a profound explanation for the high antioxidant levels in the plant.48
Tannins were also among the most frequently detected chemicals in J. schimperiana. Polyphenols are characterized by their strong affinity for proteins and metallic ions. This explains, through chemical interpretation, the traditional application of the plant in wound care and intestinal ailments, where tannins serve as natural astringents through the formation of protective layers on tissues. Their consistent presence in aqueous leaf preparations affirms that traditional water-based decoctions provide good delivery of these antioxidant and antimicrobial constituents to the patient.56 This systematic review showed that steroid-like compounds are widely distributed throughout the leaves, stem bark, and roots of J. schimperiana. The widespread distribution of steroids across all vegetative organs of J. schimperiana is a striking finding, as these metabolites are frequently linked to systemic anti-inflammatory and analgesic effects. This chemical versatility supports the plant's application across a broad spectrum of 47 different human ailments, ranging from pain management to infectious disease.57
This systematic review revealed that flavonoids are consistently present in the leaves, stem bark, and roots of J. schimperiana, having been detected across a wide variety of solvent systems including ethanol, methanol, chloroform, hexane, and aqueous preparations. The consistent detection of flavonoids (83% of studies) across various plant parts underscores their role as key therapeutic constituents. Given their established anti-inflammatory and anticancer properties, these flavonoids likely act synergistically with other polyphenols to deliver the hepatoprotective effects observed in the primary literature. Numerous flavonoids have been shown to have anti-inflammatory, antioxidant, and anticancer properties.58
This systematic review found that saponins are widely distributed across the leaves, stem bark, and roots of J. schimperiana, consistently appearing in extracts using a broad range of solvents including ethanol, methanol, chloroform, and water. The presence of saponins in 83% of the analyzed studies is a critical finding, as their ability to form complexes with membrane sterols often dictates the biological potency of medicinal extracts. Their dominance in leaf preparations suggests they are major contributors to the plant's overall pharmacological profile, potentially enhancing the absorption of other co-occurring metabolites. Saponins may prevent the body from absorbing sterol normally or may cause cell membrane damage after entering the circulation.59 Saponins were the dominant chemicals found in the leaf extracts of J. schimperiana in a recent phytochemical study.36
This systematic review revealed that alkaloids are consistently present in various leaf, bark, and root extracts of J. schimperiana across multiple solvent systems, including ethanol, methanol, chloroform, and aqueous preparations. Alkaloids are natural specialized metabolites that have nitrogen as a distinguishing ingredient in their chemical compositions. Alkaloids’ diverse atom arrangements within their chemical structures are thought to be the source of their biological power. They are found in all of the kingdoms and have a variety of chemical structures and attached functional entities, showing extensive biological characteristics.60
The review of available studies on the phytochemical analysis of J. schimperiana indicated that only 23 chemical tests have been conducted so far, which is fewer than for the plant Glycosmis pentaphylla, for which 354 chemicals have been isolated.44 It has been also noted that only few of its plant parts were examined for the chemical constituents. Plant parts such as seeds, flowers, buds, whole parts, twigs etc have not yet been tested for their chemical constituents. The available phytochemical studies on the plant did not focus on the extraction and biosynthesis of individual compounds. Consequently, a key limitation of the available data is the restricted scope of the phytochemical analysis, which has precluded a complete understanding of the plant's true chemical diversity and potential therapeutic agents. Therefore, future works shall give emphasis to the identification, isolation and characterization of individual compounds.
This systematic review revealed the presence of diverse chemical classes beyond standard secondary metabolites, including fatty acid methyl esters, essential oils, and specific isolated phenolics. The identification of 29 chemicals in root extracts and over 50 components in both leaf and root essential oils through GC-MS analysis highlights the chemical complexity of J. schimperiana.
The discovery of major components such as eucalyptol (24.13%) and espatulenol (7.25%) is particularly significant, as these compounds are known for their potent anti-inflammatory and bronchodilatory effects. This provides a clear pharmacological basis for the plant's traditional use in treating respiratory ailments. Furthermore, the first-time isolation of specific compounds like trans-resveratrol, tricuspidatol A, and kaempferol-3-O-rutinoside represents a critical advancement in the species’ phytochemical characterization. These findings indicate that while J. schimperiana is widely used in its crude form, it contains high-value bioactive molecules that justify its potential as a source for drug discovery. The variation in chemical abundance between the roots and leaves further implies that different plant parts may offer distinct therapeutic benefits, supporting the nuanced preparation methods used by traditional healers.
The pharmacological activity review of J. schimperiana indicated that the plant has promising future prospects as revealed by its active effect against the tested ailments. Its antibacterial, antifungal, antimalarial, bronchodilatory, antioxidant and anti-diabetic activities are encouraging. Additional pharmacological activity studies shall be undertaken on the hepatoprotective, antidiarrheal, antitussive, wound healing, and anti-diabetic activities. Furthermore, contradicting findings were noted in some pharmacological activities, necessitating further research for clarification. Despite the widespread traditional use of the plant for the treatment of gonorrhea, intestinal parasite, headache, skin problems, stomach-ache, and febrile illness, there is a significant gap in the literature as there is a lack of pharmacological activity study that supports its use, representing a priority area for future in vivo and in vitro studies. The higher rate of ethnomedicinal use of the plant against rabies is irrational as the pharmacological studies demonstrated only a moderate to good anti-rabies activity.
This systematic review revealed a significant disparity between the LD50 values of J. schimperiana when administered through different routes. Since intraperitoneal administration bypasses the protective mechanisms of the digestive system, which can metabolize and detoxify many compounds, it will have a more toxic effect than orally administered plants. When plant extracts are administered intraperitoneally, they are directly absorbed into the bloodstream and distributed throughout the body, leading to a higher concentration of the active compounds in the body. This can result in a more potent and toxic effect on the body, leading to a lower LD50 value. Additionally, intraperitoneal administration can cause local irritation and inflammation, which can contribute to the toxic effect. This disparity between the oral and intraperitoneal LD50 values strongly infers that the digestive system plays a protective role by metabolizing or detoxifying the active compounds, explaining the higher LD50 via the oral route.47 This could be a possible reason for the lower LD50 value observed in the study carried out by intraperitoneal injection compared to the studies done by oral administration.
This systematic review revealed that J. schimperiana is “practically non-toxic” in acute oral doses LD50 > 5000 mg/kg), which fills a critical research gap regarding the plant's basic safety profile. However, the observation of decreased hemoglobin and hematocrit at higher doses (1000 mg/kg) in sub-acute studies indicates a potential for mild hematotoxicity with repeated use.46 This finding is significant as it suggests that while the plant is safe for immediate traditional use, caution and further monitoring are required for prolonged administration to avoid impacting blood parameters.
Limitations
The overall limitations of this systematic review are the inherent heterogeneity in extract preparation, solvent choice, and in vivo models across the available studies, which complicates the direct comparison of efficacy and safety.
Conclusion
J. schimperiana is widely used for the treatment of various human ailments in all regions of Ethiopia. Liver problems, rabies, malaria, sexually transmitted disease, and evil eye were the top five human ailments treated traditionally with the use of J. schimperiana. J. schimperiana poses variety of secondary metabolites that have proven pharmacological activity against various ailments. Single dose oral toxicity studies revealed generally the plant is safe to use. This systematic review indicated that J. schimperiana has been evaluated for its antimicrobial, bronchodilator, anti-diabetic, antidiarrheal, tracheal relaxant, antitussive, anti-inflammatory, wound healing, hepatoprotective and antioxidant activities. Terpenoids, Phenols, Tannins, Steroids, Flavonoids, Saponins, and Alkaloids were the most frequently detected chemical components of the plant. In conclusion, in the majority of the studies, the LD50 of the plant was found to be greater than 2000 mg/kg. This declares the plant to be safe for a single dosage. The sub-acute toxicity study concluded the leaf extract is relatively safe at low and medium doses. However, the highest dose (1000 mg/kg) caused significant haematological changes, including reduced haemoglobin and haematocrit, and, in the 6-month chronic study, led to elevated liver enzymes and kidney function markers. Despite its widespread traditional use, the phytochemical, pharmacological, and toxicological properties of J. schimperiana are not yet fully investigated.
Supplemental Material
sj-docx-1-npx-10.1177_1934578X261433110 - Supplemental material for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review
Supplemental material, sj-docx-1-npx-10.1177_1934578X261433110 for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review by Mihretu Jegnie, Samuel Woldekidan, Bihonegn Sisay and Soressa Abebe in Natural Product Communications
Supplemental Material
sj-docx-2-npx-10.1177_1934578X261433110 - Supplemental material for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review
Supplemental material, sj-docx-2-npx-10.1177_1934578X261433110 for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review by Mihretu Jegnie, Samuel Woldekidan, Bihonegn Sisay and Soressa Abebe in Natural Product Communications
Supplemental Material
sj-docx-3-npx-10.1177_1934578X261433110 - Supplemental material for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review
Supplemental material, sj-docx-3-npx-10.1177_1934578X261433110 for Ethnomedicinal Uses, Phytochemistry, Pharmacological Activities and Toxicological Effects of Justicia schimperiana (Hochst.
ex Nees) T. Anderson: Systematic Review by Mihretu Jegnie, Samuel Woldekidan, Bihonegn Sisay and Soressa Abebe in Natural Product Communications
Footnotes
Abbreviations
Acknowledgements
The authors would like to thank the primary study authors whose research formed the basis of this systematic review.
ORCID iDs
Mihretu Jegnie
Bihonegn Sisay
Soressa Abebe
Authors’ Contribution
Conceptualization: MJ and SA; Literature search: MJ, SW, and BS; Data extraction: MJ, SW, and Bihonegn Sisay; Original draft writing: MJ, Review and editing: SA.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability
All the datasets used can be accessed from the corresponding author upon reasonable request.
Supplemental Material
Supplemental material for this article is available online.
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