Introduction

Since ancient times, one of the most common treatments has been the use of medicinal plants (Batiha et al. 2020). Due to their antioxidant, antimicrobial, and anticancer properties, as well as other biological potentials, a variety of plants are used in traditional and modern medicine (Iravani et al. 2020). The genus Salvia (Lamiaceae) includes nearly 900 species spread worldwide, with only a few species, such as Salvia africana-lutea L., being indigenous in Africa. In many African communities, Salvia africana-lutea L. is also referred to as “Sandsalie,” “Strandsalie” and “Geelblomsalie” (Mozafarian 1996). The name “Salvia” is derived from the Italian word “salvare,” which means “healer.” These plant species have been employed as ornamentals in cooking and aromatherapy and the empirical treatment of many ailments. This name was later translated into Sauja (French) and then altered to Sawge (in Old English). However, Sage has become a popular name in recent years. There was a proverb in the Middle Ages that said, “Cur moriatur homo cui Salvia crescit in horto?” (“Why should a man die if his garden has sage?”) (Dweck 2000). This demonstrates that plants in the Salvia genus have been used to treat various diseases for ages.

A recent study has shown different wild Salvia species from Iran to be economically significant because of their seeds’ high fatty acid content and potential application as fragrance sources, flavoring agents, food, and cosmetic ingredients (Moazzami Farida et al. 2016). As such, numerous representatives of the Salvia genus, including S. officinalis, S. verbenaca, S. fruticosa, and S. tomentosa, are cultivated for commercial reasons (Akhtar and Swamy 2018).

Salvia africana-lutea L. is an African indigenous species of the Salvia genus. Although the plant is a very popular medicinal botanical drug in many African countries, especially in the coastal region of South Africa, only a few scientific studies have preliminary explored the plant’s bioactivities as an antioxidant, anti-inflammatory, and antimicrobial activities (Shakeri et al. 2016). The plant is a shrubby evergreen plant with trichome projections in the leaves, which have been reported to trap valuable essential oils under its leaves. The plant has a yellow to conspicuous golden flowering that fosters its pollination by insects and hummingbirds. More information reported about the distribution, ethnobotany, and pharmacological activities of S. africana-lutea has been present in this review (Ayatollahi et al. 2009).

From a concise bibliometric analysis, only about 0.23% of reported literature on the Salvia genus is specific to S. africana-lutea. Although a few reports had information on the plant’s distribution, morphology, and ethnobotany, most studies reported the plant's diverse phytochemical constituents and therapeutic activities such as antimicrobial, antioxidant, anti-inflammatory, cytotoxic, and others (Shakeri et al. 2016. Being the first classical review on S. africana-lutea, this paper aims to foster a more in-depth study and applied research into this medicinal plant). We aim to critically examine all the available evidence about the under-explored plants, highlighting limitations, problems in the design of the studies, and future research needs. Few studies on the plant were not so detailed in their pharmacological examination of different plant extracts. Although traditionally, plants have helped alleviate inflammatory-related health conditions, the only studies on anti-inflammation were preliminary and did not show significant bioactivities. More so, the S. africana-lutea plant has been reported in many societies as edible foliage; however, there are no scientific studies on its nutraceutical application of the plants. Because of the poor level of interest in the plant, the conservation status of the plants may become worrisome and change from ‘least concern.’ Advance studies of the plant may investigate methods for improving plant propagation through in vitro cultivation and other genetic breeding protocol for an optimal cultivar.

Methodology

Studies on S. africana-lutea L. were retrieved primarily from PubMed, Scopus, and ScienceDirect databases by searching the term “Salvia africana-lutea L.” OR “Salvia aurea” OR “Crolocos aurea” OR “Salvia colorata” OR” Salvia eckloniana” (all synonymous to Salvia africana-lutea L.) across the title, abstract, and keywords published literature in the databases. Results obtained for literature specific on the S. africana-lutea were compared to a general search on reports published on other members of the Salvia genus so far, on the same databases with just the search term “Salvia.” The Google scholar database was used as a secondary search engine to ensure the study covers broad findings on the plant species. For inclusion, selected studies must be research articles that focus mainly on S. africana-lutea or Salvia aurea and must be reported in English. We excluded studies on other Salvia species, review papers, and articles in other languages apart from English.

We obtained 10 documents from PubMed, 38 from Scopus, and 10 from ScienceDirect, which focused on Salvia africana-lutea L. After an inclusion and exclusion filter, only 35 non-redundant studies were obtained as the focus of this review. From our bibliometric analysis, only about 0.23% (35/15,000+) of the total literatures published on the genus Salvia was focused on the African Indigenous Salvia africana-lutea L. as of January 2023.

Finally, using the Boolean connector “OR” and “AND” to join other keywords (antimicrobial, antibacterial, antioxidant, flowering, trichomes, analgesic, nanoparticles), studies specifically on ethnobotanical, different biological and pharmacological activities on S. africana-lutea were easily retrieved.

Ethnobotanical classification and morphology of Salvia africana-lutea L.

Salvia africana-lutea L. is an evergreen shrubby plant up to 2 m in height, indigenous to South Africa, although it may be found in other African and Asian countries (Rattray and Van Wyk 2021). Generally, the plants have various common names based on their morphology as well as differences in vernacular. Some of these common names are golden Salvia (due to its yellowish golden petals), dune Salvia (due to its flower and leave shape), beach Salvia (due to its common coastal location), and wild sage and sand sage. Other vernacular names common with many South African societies are Sandsalie, Geelblomsalie, Strandsalie, and Bruinsalie (Foden and Potter 2005a; Viljoen and Notten 2019a).

S. africana-lutea is classified under “least concern” to its conservation status due to its widespread nature, abundance, and lower risk of extinction (Foden and Potter 2005b). The plants grow in coastal and sandy areas and have shown excellent resistance to drought or limited water. The plants are very hardy, with aromatic grey-greenish leaves and unique clusters of brown funnel-shaped flowers (Fig. 1). The plant begins flowering in early spring with bright yellow flowers, which mature in June (having a rusty-orange color) and finally fade to reddish-brown in December. The conspicuous nature of the flowers producing nectar makes them attractive for insect/sunbird pollination (Wester and Claßen-Bockhoff 2006; Wester 2013). Faded flowers fall off., leaving a nicely purple-colored calyx (Strelin et al. 2017).

Fig. 1
figure 1

A snapshot of Salvia africana-lutea L. whole plant. The plant is shrubby with grey-green leaves up to 2 m in height. It has golden petals (hence sometimes called “golden salvia”) and a unique dune-shaped/funnel-shaped flower and leaves (dune salvia). Faded flowers fall off, leaving a nicely purple-colored calyx

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The name Salvia. africana-lutea is also synonymous with Salvia. aurea L., Crolocos aurea (L), Salvia colorata (L) and Salvia eckloniana Benth (Retrieved from Royal Botanical Garden, Kew Science). The plant belongs to the Lamiaceae (Labiatae) family, commonly referred to as the sage family, which are well-known for their square stems, aromatic and opposite leaves, bilaterally symmetrical flowers bearing four stamens, and ovaries with two fused carpels (Rattray and Van Wyk 2021). The plant name “Salvia. africana-lutea” or “S. aurea” is derived from the Latin description of its characteristics; for instance—Salvia is from the Latin word Salvere (which means to save or heal based on its medicinal properties) and aurea, which means golden (Latin words to describe its flower color). The new name, according to Linnaeus’s system of taxonomy, “S. africana-lutea,” describes the plant's origin in Africa (africana) and its characteristic golden flowers (lutea) (Viljoen and Notten 2019b). The modern taxonomical classification of S. africana-lutea is summarized below.

Taxonomical classification of S. africana-lutea

Kingdom:Plantae

Phylum:Tracheophytes

Sub-phylum:Angiosperms

Class:Eudicots

Subclass:Asterids

Order:Lamiales

Family:Lamiaceae

Genus:Salvia

Species:S. africana-lutea

The Salvia genus is made up of plants with characteristic hair-like trichomes. A few studies have reported the presence of glandular and non-glandular trichomes (a form of outgrowths) on the leaves surface of different members of the Salvia genus from microscopy analysis. Specifically, Kamatou et al. (2006) reported that S. africana-lutea showed non-glandular trichomes on their leave surface, consisting of elongated, unbranched, and multicellular cells. However, another study identified two types of glandular trichomes: the peltate gland and the capitate trichome. The peltate gland is characterized by a short stalk and multiple large cell-head, whereas the capitate trichome shows two sub-type (type 1 and II) (Serrato-Valenti et al. 1997). Type I had a monocellular stalk and a bicellular head, while type II had a multicellular stalk, a neck cell, and a unicellular head. In the study, the peltate gland and the Type 1 trichome were more ubiquitous across S. africana, while Type 11 capitate trichomes were sparsely dispersed (Serrato-Valenti et al. 1997). This morphological feature (hair-like trichomes) is an interesting taxonomical distinguishing feature of different members of the Salvia genus (Kamatou 2006).

A histochemical study reported that the role of these multi-classed glandular trichomes is to trap and prevent the loss of S. africana-lutea essential oil (Serrato-Valenti et al. 1997). Moreover, the trichome was also implicated in secreting bio-macromolecules such as polyphenols, polysaccharides, and other bioactive polypeptides. There is a need for more in-depth studies on other morphological features of S. africana-lutea plants to fill the missing gaps in the body of knowledge.

Traditional uses

Salvia genus has been used in the treatment of different disorders such as sore throats, common cold, flu, night sweats, tuberculosis, menopause (against sweat flushes), and some cancers, and used to cure some heart diseases such as angina pectoris, myocardial infarction in China (Russo et al. 2016, 2018; Fotovvat et al. 2019). This genus has been used as a disinfectant for wounds, as a diuretic, stomach tonic, antiflatulent, and reconstituent, and for the treatment of eye disorders, diarrhea, dyspepsia, fever, rheumatism, excessive menstruation, coughing, pertussis, sinusitis (Moazzami Farida et al. 2016), psoriasis, seborrhoeic eczemas (Jantová et al. 2014), bronchitis, pyretic, rheumatoid arthritis, colds, wounds and skin infections, headache, cerebral ischemia, and memory disorders, including hepatitis (Fotovvat et al. 2019) and malaria, inflammation, loss of memory and disinfecting homes after sickness (Kamatou et al. 2008a, b, c). Salvia genus members were also employed to increase women’s fertility, ward off evil spirits, and heal snake bites, among other things (Dweck 2000; Bakir et al. 2020).

S. Africana-lutea, also known as beach sage, golden sage, or S. aurea, is one of the most important species used by traditional healers. Leaf decoction is generally used to treat coughs, colds, and ailments related to women (Scott et al. 2008; Van Wyk and Gorelik 2017). The first European settlers used S. africana-lutea aqueous extracts of the leaves to treat colds, tuberculosis, and chronic bronchitis. Traditional indigenous healers use ethanol extracts (maceration in concentrated ethanol/dry gins) to treat respiratory problems, influenza, gynecological concerns, fever, headaches, and digestive disorders (Watt & Breyer-Brandwijk 1967; Kamatou et al. 2008a, b, c). The whole plants and sometimes the leaves of S. africana-lutea are traditionally used as an infusion (maceration in water at room temperature) in South Africa to treat colds, tuberculosis, chronic bronchitis, influenza, gynecological complaints, fever, headaches, and digestive disorders (Kamatou et al. 2010; Arief et al. 2018; Rattray and Van Wyk 2021). Focused information on the traditional uses of S. africana-lutea is sparse and still superficial. Therefore, we recommend a detailed ethnopharmacological study of the underexplored plant in different societies in Africa and the world.

Phytochemical constituents of S. africana-lutea

Phytochemical investigations on S. africana-lutea have shown the presence of different bioactive constituents, as summarized in Table 1. Researchers have isolated and characterized bioactive constituents from the aerial parts of this plant and systematically evaluated them for different pharmacological activities. These constituents include non-volatile and volatile metabolites from essential oils obtained from S. africana, analyzed by gas chromatography-mass spectrometry (GC–MS) and gas chromatography with a flame ionization detector (GC–FID) (Bisio et al. 1998a, b). This analysis shows that monoterpenes, diterpenes, triterpenes, and sesquiterpene were the primary active metabolites (Figs. 2, 3, 4 and 5) (Najar et al. 2021). Like other botanical drugs, the bioactive metabolites of S. africana varies depending on the part of the plant used, the collection zone, and environmental conditions such as water availability, altitude, and climate (Russo et al. 2013). Hence, future studies may opt to properly report phytochemical/bioactive metabolites from S. africana and the variation in their relative abundance. The metabolites isolated from S. africana forms valuable resources for designing new drugs and disease treatment (Calderón-Oropeza et al. 2021). The primary metabolites identified from S. africana and their class of metabolites are summarized in Table 1.

Table 1 Main Chemical metabolites isolated from S. africana-lutea
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Fig. 2
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Phenolics present in S. africana-lutea. (1) Salvianolic acid K; (2) Rosmadial; (3) Rosmarinic acid; (4) Salvianolic acid B; (5) 2,4-Dimethyl Benzenepropanoic acid; (6) Quinic Acid; (7) Danshensu; (8) Caffeoyl Acid; (9) Yunnaneic acid E (isomer 1–6); (10) Hydroxy-Luteolin–Glucuronide; (11) Yunnaneic acid F; (12) Yunnaneic acid D (isomer 1–2) (13) Luteolin-7-O-Glucuronide (14) Sagerinic Acid (isomer 1) (15) Caffeoyl Rosmarinic acid (isomer 1–3); (16) Thymol; (17) Carvacrol; (18) (Z)-Isoeugenol;

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Fig. 3
figure 3

Di and triterpenes of S. africana-lutea. (19) Carnosol; (20) Carnosic acid methyl ester; (21) Methyl carnosate; (22) 7-methoxyrosmanol; (23) Oleanolic; (24) Ursolic acids; (25) β-amyrin; (26) Propanoic acid; (27) Rythronic acid; (28) 2-keto-1-gluconic acid; (29) Terpinene-4-ol; (30) β-caryophyllene; (31) Ursolic acid

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Fig. 4
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Monoterpene of S. africana-lutea. (32) Tricyclene; (33) α-Thujene; (34) Sabinene; (35) β-Pinene; (36) δ-3-Carene; (37) α-Terpinene; (38) p-Cymene; (39) Limonene; (40) (Z)-β-Ocimene; (41) γ-Terpinene; (42) 1,8-Cineole; (43) Cis-Sabinene hydrate; (44) Hydrate; (45) Cis-Thujone; (46) Trans-Thujone; (47) Cis-p-Menth-2-en-1-ol; (48) Camphor; (49) Pinocarvone; (50) Borneol; (51) Terpinen-4-ol; (52) p-Cymen-8-ol; (53) α-Terpineol; (54) Verbenone; (55) Trans-Carveol; (56) Bornyl acetate

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Fig. 5
figure 5

Sesquiterpene of S. africana-lutea. (57) α-Cubebene; (58) α-Gurjunene; (59) β-Caryophyllene; (60) Aromadendrene; (61) β-Gurjunene; (62) α-Guaiene; (63) α-Humulene; (64) γ-Gurjunene; (65) Germacrene D; (66) Cis-β-Guaiene; (67) Valencene; (68) α-Muurolene; (69) β-Himachalene; (70) γ-Cadinene; (71) Selina-3,7(11)-diene; (72) δ-Cadinene; (73) T-cadinol; (74) Germacrene B; (75) Cubebol; (76) Germacrene D-4-ol; (77) Caryophyllene oxide; (78) Globulol; (79) Viridifloro; (80) 1-epi-Cubenol; (81) τ-Cadinol; (82) α-Eudesmol; (83) β-eudesmol

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Pharmacological properties of S. africana-lutea extracts and phytochemicals

Most of the available studies on Salvia africana-lutea L. have reported some preliminary but interesting pharmacological bioactivities of its extracts and phytochemicals, such as its activities in suppressing inflammation, oxidation, microbial infection, and related disorders. We have discussed each of its biological activities in the following section (Fig. 6).

Fig. 6
figure 6

An overview of some biological activities of Salvia africana-lutea L. and its phytoconstituents. A few studies on S. africana-lutea and its phytoconstituents show different bioactivities such as antioxidant, anti-inflammatory, antimicrobial, and others

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Suppression of inflammation by S. africana-lutea extracts and phytochemicals

S. africana-lutea has been demonstrated to possess phytochemicals that can modulate immune systems response (e.g., suppress the production of inflammatory mediators and suppress mast cells’ infiltration) (Maione et al. 2017; Ahmed et al. 2021; Sina Içen et al. 2021). Mast cells play essential roles in the initiation and sustainment of inflammation (Yousef et al. 2020); leukotrienes, one of its granules’ contents, contribute to the attraction of eosinophils into the airways where they cause/exacerbate chronic obstructive pulmonary diseases (Lee et al. 2021), while prostaglandins (another granules’ content) have been implicated in tumorigenesis (Wang et al. 2021b) other neuropsychiatric and cardiovascular disorders, reviewed in (Famitafreshi and Karimian 2020; Wang et al. 2021a). In mammals, leukotrienes and prostaglandins are biosynthesized from arachidonic acid in a series of reactions initiated by 5-lipoxygenase (5-LO) and cyclooxygenases(COX)-1/COX-2 respectively, reviewed in (Wang et al. 2021a, b; Giménez-Bastida et al. 2021); and inhibiting these key enzymes are the mechanisms of action of many anti-inflammatory agents, including aspirin, ibuprofen, nordihydroguaiaretic acid (NDGA) and zileuton (Famitafreshi and Karimian 2020; Wang et al. 2021a; Altinbas et al. 2021; Drago et al. 2021). Because of some of these drugs (Turpeinen et al. 2021; Bouchette and Preuss 2021), there is a need to discover other and more suitable anti-inflammatory agents, and some constituents of S. africana-lutea have potential. Essential oil from S. africana-lutea aerial parts inhibited 5-lipoxygenase activity (IC50 = 77.3 µg/ml). However, it has very low therapeutic potential as it is very toxic to transformed human kidney epithelial cells (IC50 < 7 µg/ml), and its effectiveness at inhibiting 5-lipoxygenase also pales when compared to that of the reference anti-inflammatory drug NDGA (IC50 = 5.0 µg/ml) (Kamatou et al. 2006). A similar poor inhibitory effect on 5-lipoxygenase (IC50 > 100 µg/ml) by the methanol: chloroform extract of S. Africana-lutea aerial parts was also observed by the same research group (Kamatou et al. 2010). Apart from the preliminary anti-inflammatory studies on the plant conducted by Kamatou et al. (2010), there has been limited information on the key bioactivities necessary for some of the most mentioned traditional usage. Other deductions on the anti-inflammatory activities can be made from a few anti-inflammatory studies on its specific and abundant phytochemicals. For instance, the phytochemical rosmarinic acid methyl ester (syn. methyl rosmarinate) abundant in S. africana-lutea (Arief et al. 2018) and some other Salvia species (Kamatou et al. 2012a; Sina Içen et al. 2021) showed interesting in-vitro lipoxygenase inhibitory activity (IC50 = 0.02 µM = 8.23 µg/mL) that is similar to that of NDGA (IC50 = 0.03 µM = 11.62 µg/mL) (Sina Içen et al. 2021).

The enzyme microsomal prostaglandin E synthase-1 (mPGES-1) is involved in the production of prostaglandin E, a pro-inflammatory molecule. Carnosol (CS) and carnosic acid (CA), both present in S. africana-lutea (Kamatou et al. 2010; Arief et al. 2018), inhibited mPGES-1 activity in cell-free microsomes (IC50 of both = 5 µM) while CA (but not CS) inhibited the lipopolysaccharide-induced formation of PGE2 in whole blood (IC50 = 9.3 µM) (Bauer et al. 2012). The effectiveness of CA is comparable to that of mPGES-1 reference inhibitor MD-52 (3 µM of CA reduced PGE2 synthesis in whole blood by 35%, while 2 µM of MD-52 inhibited PGE2 synthesis by 44%). 10 μM indomethacin (reference COX inhibitor), on the other hand, reduced PGE2 synthesis by 81% (Bauer et al. 2012). In another study, both CA and CS in cell‐free assays inhibited the formation of 5-LO products (IC50 = 0.8 and 0.3 μM respectively) and also inhibited mPGES-1 activity (IC50 = 14.0 and 10.9 μM respectively) (Maione et al. 2017). Rosmarinic acid (RA), a popular S. africana-lutea phytochemical (Kamatou et al. 2010; Lim Ah Tock et al. 2021), on the other hand, had a poor inhibitory effect on lipoxygenase (IC50 = 0.21 µM = 76 µg/mL), when compared to reference drug NDGA (IC50 = 0.03 µM = 11.62 µg/mL) (Sina Içen et al. 2021), and was unable to inhibit PGE2 formation in whole blood (Bauer et al. 2012).

In in-vivo models, however, the anti-inflammatory effects of RA, through different mechanisms, were more pronounced, though not without reservations. Wistar rats treated with rosmarinic acid (RA) showed fewer signs of inflammatory damage when exposed to the toxic pesticide malathion (MA) (Ahmed et al. 2021). RA (50 mg/kg b.w./day) was co-administered by gavage with MA (100 mg/kg b.w./day) for 3 weeks. It resulted in a 90% lower histopathological scoring of the lungs, 83.5% lower mast cell infiltration, 64.4% reduction in survivin expression, and 400% increase in pulmonary surfactant protein D (SP‐D) expression in the treated group compared to those that received only MA. Mast cells activation has been implicated in acute lung injuries (Chen et al. 2021); survivin expression level has been positively correlated with acute lung injuries (Ahmed et al. 2019), while SP-D level has been negatively correlated with the number of apoptotic pneumocytes (Du et al. 2018; Cañadas et al. 2020). The ability of RA to suppress mast cell infiltration and survivin level while upregulating SP-D level proves that RA has anti-apoptotic effects and potential that can be harnessed for developing anti-inflammatory agents. However, its effectiveness in the in-vivo study by Ahmed et al. (2021) was not compared to that of any anti-inflammatory drug; and it has been demonstrated that RA, in a different study, decreased the viability of mast cells to 73.5% of the control (Yousef et al. 2020). Thus, the application of RA as an anti-inflammatory agent should be encouraged only after confirming that its suppression of mast cells' viability does not predispose the body to greater danger.

Antioxidant effects of S. africana-lutea extracts/ phytochemicals and potentials for preventing melanin-related disorders

Salvia africana-lutea L. extracts and phytochemicals have been credited with alleviating oxidative stress by suppressing radicals’ production or scavenging already-produced ones. Aqueous extract of S. africana aerial parts, through the unstudied mechanism, inhibited lipopolysaccharide-induced nitric oxide production in macrophages (EC50 = 47.8 µg/mL). However, it was not as effective as dexamethasone's reference product (EC50 = 16.0 µg/mL) (Afonso et al. 2019). The solvent extracts of S. africana-lutea also showed good potential to different radicals such as DPPH and ABTS scavenge radicals with IC50 or EC50 values ranging from 6.6 to 62.0 µg/mL, depending on the assay method (Kamatou et al. 2008c, b, 2010; Afonso et al. 2019), the composition of the extract (with or without the essential oil) (Kamatou et al. 2008b) and the season of plants collection (Kamatou et al. 2008c) (see Table 2). The extracts all displayed significantly lower activity than the positive controls (Kamatou et al. 2008b, 2008c, 2010; Afonso et al. 2019). In some of these studies, the antioxidant activities were accessed only by some checking out in vitro chemical analyses such as DPPH and ABTS radical scavenging activities. For instance, Kamatou et al. (2010) investigated the radical scavenging activities of chlorofoam/methanol extract (1:1) of 16 South African indigenous Salvia species, of which S. Africana is inclusive, using the DPPH and ABTS assays. This study merely compared their IC50 of the different plant extract, without critically evaluating if these activities are of clinical or pharmacological relevance. There have been recent debates on these analyses’ insufficiencies in giving reliable and credible evidence on the antioxidant capacity of the plant extracts (de Menezes et al. 2021). However, these analyses could give a possible clue to the antioxidant capacity. There is a need for other in vivo or multiple in vitro analyses to give more robust evidence of an extract’s antioxidant capacity, which can be of more pharmacological relevance.

Table 2 summary of the antioxidant, anti-inflammatory, anti-diabetic and analgelsic effects of S. africana-lutea extracts and phytochemicals
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The phytochemicals: 19-acetoxy-12-methoxycarnosic acid, 3β-acetoxy-7α-methoxyrosmanol, and clinopodiolides A isolated from the methanol extract of S. africana-lutea aerial parts exhibited high antioxidant activities (2588.2, 2233.9 and 2357.2 µmole TE/g respectively, as determined by Oxygen Radical Absorbance Capacity assay), which were comparable to that (3976.8 µmole TE/g) of epigallocatechin gallate, the reference product (Etsassala et al. 2019).

The antioxidant potentials of S. africana-lutea extracts and phytochemicals, however, are not limited to their abilities to scavenge radicals but also extend to their abilities to inhibit oxidizing enzymes, which has good potential for preventing/managing melanin-related disorders. Melanin is a heterogenous light-absorbing polymer containing indoles and other intermediate products of tyrosine oxidation, which plays a role in thermoregulation and protects human skin by absorbing/reflecting UV radiation; and scavenging reactive oxygen species (ROS), toxic drugs, and chemicals (Momtaz et al. 2008; Maranduca et al. 2019; Cao et al. 2021; McNamara et al. 2021). Its formation is radical-dependent and can be facilitated by exposure to UV radiation and iron (Momtaz et al. 2008; Hedges et al. 2020). Hyper-accumulation, especially in specific skin parts, as more pigmented patches (e.g., melasma, freckles, ephelides, etc.) becomes an aesthetic problem (Momtaz et al. 2008). Reducing the production of melanin by melanocytes has found applications in the cosmetics industry for skin-lightening effects, which can be achieved by, among other means, inhibiting the activities of tyrosinase, which catalyzes the hydroxylation of monophenols (L-tyrosine) to O-diphenols (DOPA) and the oxidation of the O-diphenols to O-quinones (DOPA quinone), essential steps in melanin biosynthesis (Momtaz et al. 2008; Ha et al. 2012; Asghari et al. 2019). Also, hyperactivity of tyrosinase has been implicated in Parkinson’s disease, a neural disorder whereby the accumulation of neuromelanin, reactive oxygen species (ROS), and other tyrosinase catalyzed- dopamine oxidation products promote aging and death of dopaminergic neurons (Zhang et al. 2019; Maranduca et al. 2019). S. africana-lutea extracts and phytochemicals inhibit tyrosinase activity, and some have the potential for therapeutic applications. Methanol extract of S. africana-lutea aerial parts at 500 µg/ml in an in-vitro study inhibited tyrosinase activity by 48% and DOPA auto-oxidation by 36% (Momtaz et al. 2008). Its activity was, however significantly less than that of the reference products arbutin (tyrosinase IC50 = 149 µg/ml) and kojic acid (tyrosinase IC50 = 2.145 µg/ml and DOPA IC50 = 26.66 µg/ml). In a study that measured the ability of RA and methyl rosmarinate to inhibit tyrosinase oxidation of L-DOPA, 0.4 mM each of RA and methyl rosmarinate reduced activity by 19.8 and 37.1%, respectively (Lin et al. 2011). In another study, RA inhibited L-DOPA oxidation with an IC50 value of 6.67 μM (Zuo et al. 2018), which is close to the reported IC50 value of 4.0 μM, when RA was used as a substrate for tyrosinase reaction (Ha et al. 2012). In the above studies, the inhibitory effects of the phytochemicals were not compared to those of any reference antioxidant agents. In an earlier study that used L-tyrosine as the substrate, RA and methyl rosmarinate inhibited tyrosinase oxidation of L-tyrosine with IC50 values of 16.8 and 21.5 μM, respectively, which were similar to or marginally better than the activity of reference tyrosinase inhibitor kojic acid (IC50 = 22.4 μM) (Kang et al. 2004). We thus suggest that these two phytochemicals should be considered for therapeutic applications. We could also see that the reported IC50 values from different researchers varied widely (e.g., 4.0 μM to 16.8 μM for RA). This may be due to the differences in the choice of substrates.

Anti-diabetic effects of S. africana-lutea extracts and phytochemicals

Diabetes, a disease characterized by chronic blood hyperglycemia due to inefficiencies in insulin production and/or utilization (Ezeorba et al. 2022), accounts for about 1.5 million deaths annually; is currently affecting about 422 million individuals (World Health Organization 2021) and is expected to affect about 700 million individuals by the year 2045 (Kaur et al. 2021). During type 2 diabetes, caused by insulin resistance, the body cannot use glucose as a source of energy. Hyperglycemia predisposes the body to stroke (Hill 2014), heart failure (Tochiya et al. 2020), obesity (Bentley et al. 2020), foot ulcers (Awasthi et al. 2020), diabetic retinopathy (Antonetti et al. 2021), diabetic nephropathy (Cheng et al. 2020), diabetic neuropathy (Jensen et al. 2021), etc. Reducing postprandial blood glucose levels and increasing glucose uptake into muscle, adipose, or liver cells reduces complications of type 2 diabetes (Etsassala et al. 2019, 2020). Ursolic and oleanolic acids isolated from methanol extract of S. africana-lutea aerial parts respectively inhibited alpha-glucosidase (IC50 = 11.3 µg/mL) and alpha-amylase (IC50 = 12.5 µg/mL) activities (Etsassala et al. 2019). They were non-toxic to human cells even at 250 µg/mL (Etsassala et al. 2020). Their enzymes' inhibitory effects were comparable to or even better than that of the reference agent, acarbose (alpha-glucosidase IC50 = 610.4 µg/mL; alpha-amylase IC50 = 10.2 µg/mL), highlighting their potential as anti-diabetic agents. Alpha-amylase breaks down complex polysaccharides to produce oligosaccharides and disaccharides, which are further hydrolyzed by alpha-glucosidase to absorb monomeric units (Etsassala et al. 2019; Zhang et al. 2020). These enzymes are unique targets for the prevention and treatment of type 2 diabetes (Zhang et al. 2020; Kaur et al. 2021), and by inhibiting them, the phytochemicals of S. africana-lutea delay carbohydrates absorption and reduce postprandial blood glucose levels. In another study, 100 µg/mL of 19-acetoxy-12-methoxycarnosic acid, clinopodiolides B, and ursolic acid, also isolated from methanol extract of S. africana-lutea aerial parts, increased glucose uptake into mammalian cells (thereby reducing insulin resistance) by 62.5, 55 and 45% respectively, compared to untreated cells (Etsassala et al. 2020). 19-acetoxy-12-methoxycarnosic acid and clinopodiolides B, however, had lower therapeutic potentials when compared to ursolic acid as they, unlike ursolic acid, reduced the viability of human embryonic kidney (HEK293) cells by 62 and 48% respectively at 250 µg/mL, compared to untreated cells (Etsassala et al. 2020). The toxicity of 19-acetoxy-12-methoxycarnosic acid and clinopodiolides B do not adversely limit their potential since their maximum tested concentration that increased glucose uptake (100 µg/mL) is still significantly lower than the tested toxic dose of 250 µg/mL. However, the glucose uptake efficiencies of these phytochemicals were not compared to any referenced product.

Analgesic/anti-nociceptive and antipyretic effects of S. africana-lutea extracts and phytochemicals

Pain is a distressing sensory or emotional occurrence correlating to existing or potential tissue damage (Raja et al. 2020). It can be physiological (nociceptive and/or inflammatory) or pathological (neuropathic and central nervous system dysfunctional) pain (Fong and Schug 2014). Nociceptive and inflammatory pains are protective and adaptive, encouraging withdrawal from noxious mechanical, thermal and chemical stimuli or protecting damaged but healing body tissues (Gangadharan and Kuner 2013; Fong and Schug 2014; Baral et al. 2019; Liu et al. 2021). Pathological pain, on the other hand, is chronic, non-protective, and maladaptive, serving as a life-impacting symptom of a disease or nervous system damage (Gangadharan and Kuner 2013; De Goeij et al. 2013; Fong and Schug 2014; Baral et al. 2019; Liu et al. 2021). Prostaglandins have been implicated in lowering the firing threshold of sensory neurons, promoting hyperexcitability, and increasing the number of action potentials generated by a stimulus (Jang et al. 2020; Liu et al. 2021; Kwon et al. 2021). This is probably by increasing the expression of Nav1.7 (Zhang and Gan 2017), the master Na+ channels, which relay nociceptive signals to the central nervous system (Gangadharan and Kuner 2013), making usually painless stimuli painful. The deletion of mPGES-1 has been associated with an increase in pain threshold (Jang et al. 2020). Thus, reducing the levels of prostaglandins will be a good analgesic strategy, and it will help in ameliorating the conditions of many patients in a study that measured the frequency of intraperitoneally-injected acetic acid-induced writhing in mice (Amabeoku et al. 2001), 15 min of prophylactic intraperitoneal (i.p). Injection with 200 and 400 mg/kg water extracts of S. africana-lutea leaves reduced the writhing frequency by 61.45 and 58%, respectively, compared to those that received only acetic acid. Paracetamol, the reference product, was more effective at reducing the number of writhes (96.7% compared to those that received only acetic acid). At 55 °C, 15 and 30 min i.p. prophylaxis with 200 mg/kg extracts, in the same study, increased the time to thermally induced pain threshold by 84.1 and 91.7%, respectively; while 400 mg/kg increased that by 99.1 and 100% respectively, compared to those treated i.p. with normal saline. This was unlike paracetamol (300–500 mg/kg, i.p.) which did not affect thermally induced pain. 15 min of prophylaxis with 100, 200, and 400 mg/kg reduced lipopolysaccharide-induced temperature increases by 1.75, 2.31, and 2.08 °C, respectively, unlike 500 mg/kg (i.p) paracetamol that did not affect lipopolysaccharide-induced fever. However, the above-described studyr, did not study the mechanism through which the extracts exerted their effects. In another study, by inhibiting the formation of 5-LO products by CA and CS (IC50 = 0.8 and 0.3 μM respectively) and also by inhibiting mPGES-1 activity (IC50 = 14.0 and 10.9 μM respectively), 100 g/l subcutaneously (s.c)-injected CA and CS were able to reduce 50 µl 1% s.c. Carrageenan-induced hyperalgesia in mice by 43.7 and 47%, respectively, compared to mice treated with only the vehicle (50 μl saline s.c.) (Maione et al. 2017). These indicate that S. africana-lutea extracts and phytochemicals have potentials that may be exploited for the development of analgesics.

Antimicrobial and anti-parasitic activities of S. Africana-lutea

Microbes are double-edged, as they can benefit humans and could become a source of severe trouble and health challenges (Weiman and Fox 2015). Pathogenic microbial groups represent all disease-causing bacteria, fungi, and parasitic protozoans known to cause physiological or metabolic distortion to the normal state of the human body (Najar et al. 2021). The battle for survival between these pathogenic organisms and humans has existed for many decades. Humans have constantly searched for effective antimicrobial (antibacterial, antifungal, anti-protozoan, or anti-parasitic) agents. In contrast, pathogens constantly evolve new mechanisms to resist these agents (Imperial and Ibana 2016). Plants have been reported as a reservoir for interesting metabolites and phytochemicals, which have proven effective antimicrobials (Savoia 2012). Traditionally, these metabolites and phytochemicals are enriched in different plant parts and are concentrated by different extraction solvents (yielding crude extract). Moreover, scientific advances have led to the development of protocols for the selective enrichment or purification of a single plant metabolite with known antimicrobial functions (Atanasov et al. 2015, 2021). Salvia species is one of those few plant genera showing interesting antimicrobial activities (Sharifi-Rad et al. 2018; Shirinda et al. 2019; Zaccardelli et al. 2020; Ezema et al. 2022). From our literature search, more than 1000 recent studies have focused on characterizing the antimicrobial activities as well as other bioactivities of different Salvia species. In contrast, only a few (about five articles) have focused on the indigenous African species—S. Africana-lutea (Table 3). The section extensively reviewed all the studies on the antimicrobial activities of S. africana to project its potential for exciting bioactivities to the global scientific community and draw attention to the need for more studies on this African indigenous Salvia sp. to harness other unraveled benefits fully.

Table 3 Antimicrobial activities of S. Africana-lutea
Full size table

Antibacterial activities

A few studies on S. Africana-lutea have shown its antibacterial potencies on pathogenic strains (Table 3). A recent study by Afonso et al. (2019) reported that 100 µL aqueous extract of S. africana-lutea at 1:400 dilution caused significant inhibition of S. aureus and S. epidermis. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were estimated to be 0.63 and 1.25, respectively (Afonso et al. 2019). Recently, Dube et al. (2020) reported improved antibacterial activities against Staphylococcus epidermidis and Pseudomonas aeruginosa when the aqueous extract of S. africana was delivered with silver nanoparticles (MIC: 0.1875 mg/ml and 0.375 mg/ml, respectively) (Dube et al. 2020).

In another study, the methanol extract of the whole S. africana plant (comprising its leaves, stems, and flowers) was reported to cause inhibition of the growth of pathogenic bacteria, Escherichia coli, and Staphylococcus aureus, as well as the fungi, Microsporum audouinii, all having a minimum inhibitory concentration (MIC) of 39.06 μg/ml (Nielsen et al. 2012). An extract or bioactive molecule is an effective antimicrobial agent if the MIC falls below 1 mg/mL or 1000 μg/ml. Judging from this standard, the antibacterial and antifungal activities reported by Nielsen et al. (2012), extract of S. africana-lutea are effective antibiotics. They can be developed for treating and managing debilitating conditions caused by those microbial agents.

The essential oil of Salvia Africana L. was recently extracted through hydro-distillation and characterized using gas chromatography coupled with Mass Spectrometry (Kamatou et al. 2006). The abundance of the constituents of the essential oils, as well as the antimicrobial activities, was reported. An aliquot of 100 μL of 1:100 dilution of essential oil showed enjoyable inhibitory activities against spore-forming gram-positive bacteria (Brevibacillus sp.), which are frequently implicated in the foot odor disorder (bromodosis) (Kamatou et al. 2006). The MIC result for B. agri, B. epidermis, and B. linens was reported to be 0.13, 0.50, and 1.00 mg/mL, respectively, showing the efficacy of S. africana essential oil-rich fraction in managing the foot odor disorder (Kamatou et al. 2006).

Finally, it was recently shown that the ethanolic extract of S. africana-lutea was potent against mycobacterium sp. for managing tuberculosis (Oosthuizen et al. 2019). Tuberculosis is ranked as the second leading source of death globally due to the invasiveness of its causative agent. S. africana-lutea was among the three plants screened out to possess significant anti-mycobacterium activities. The study reported that S. africana-lutea ethanolic extract gave a minimal inhibitory concentration (MIC) of 31.25 μg/ml against Mycobacterium smegmatis from a “microplate Alamar Blue assay” and EC50 of 95.8 μg/ml against the initiation of biofilm (Oosthuizen et al. 2019). An older study isolated and characterized a derivative of carnosic acid from the ethanoic extract of S. africana-lutea, which showed a MIC of 28 µM against Mycobacterium tuberculosis using the rapid radiometric method (Hussein et al. 2007). Both studies showing anti-mycobacterium activities also showed cytotoxic, apoptotic, and anticancer activities against human breast cancer (MCF-7) and U937 human macrophage cell lines (Hussein et al. 2007; Oosthuizen et al. 2019). Details report of the anticancer activities of S. africana-lutea and other Salvia sp. was recently reported in a review by Ezema et al. (2022).

Antifungal activities

There are only a few studies on the antifungal activities of S. africana-lutea. As aforementioned, Nielsen et al. (2012) studies reported a potent inhibition of Microsporum audouinii by the methanol extract of S. africana. Using the micro broth dilution method over a test concentration of 19.53 to 2500 μg/ml, an MIC of 39.06 μg/ml was obtained (Nielsen et al. 2012). Another study by (Nkomo et al. 2014) reported that Dichloromethane: methanol (1:1; v/v) extract of S. africana lutea at a test concentration between 0.002 and 1 mg/ml showed antifungal activities against Fusarium verticillioides and Fusarium proliferatum at a minimum inhibitory concentration of 0.031 mg/ml and 0.063 mg/ml respectively (Nkomo et al. 2014). These two studies have shown the promising antifungal activities of S. africana-lutea. Ever since the last study in 2014; there have been no other reports on the antifungal activities of S. africana. Hence, future studies could further investigate the inhibitory effects of different solvent extracts or purified phytochemicals of S. africana on other pathogenic fungal strains.

Prospects for anti-parasitic activities and future studies

Despite the global awareness of the health, nutritional and therapeutic benefits of S. africana-lutea, no studies have investigated the anti-parasitic activities of S. africana. Moreover, a number of studies have shown the efficacies of other varieties of Salvia Sp. to inhibit many parasites and protozoan, including Trypanosoma sp., Schistosoma sp., Leishmania sp., Plasmodium sp., and others (Akkawi et al. 2012; Amirmohammadi et al. 2014; Tariq et al. 2016; Montesino and Schmidt 2018; Tabefam et al. 2018). Therefore, studies need to investigate the efficacies of the S. africana-lutea strain on parasites and protozoans, especially against Plasmodium sp., causing malaria infection, which is predominant in Africa.

Going a step further, studies should also be directed toward investigating the potential of this Africa-indigenous Salvia sp. on ameliorating or curbing the increase of antibiotic resistance microbial strains and superbugs causing the rise in microbial infection mortality rate. Similarly, modern analytical and computation tools could be applied to purify and characterize the bioactive component from S. africana responsible for its exciting bioactivities.

Conclusion and prospect for future research

Salvia africana-lutea L. is an indigenous African member of the Salvia genus, which has been poorly explored research-wise. We have reviewed all studies published on the plants with the most focus on their ethnobotanical features, phytochemical composition, and pharmacological activities. There is a need for more research focus to be redirected towards this plant species for better characterization of its bioactive metabolites for medicinal purposes and drug discovery.

Scientific literatures on the traditional usage of the plant are superfluous. More detailed ethnopharmacological reports are needed in the future on the usage of the different parts of the plants (their preparation and concentration) for alleviating health challenges by different societies of the world. More so, despite pieces of information about the plant's edible nature, there are sno astute scientific studies detailing the nutraceutical application of the plants, although this may be closely related to their pharmacological application. It is also worth mentioning that there are no studies on bioavailability and toxicity. This is another future research that needs a more holistic understanding of the plant's true pharmacological bioactivities.

It is also surprising that despite the antimicrobial activities as well as cytotoxic activities of the plant, there have not been any studies to investigate the anti-COVID potential of the plant since the onset of the last pandemic. In silico and in vitro approaches can be adopted for future investigation of the potencies of S. Africana-lutea against Coronaviruses (COVID-19).

More so, future studies could investigate more into the potencies of green synthesized nanoparticle from the S. africana-lutea, as plant-derived nano-materials promises a lot in modern medicinal research. One available study by Dube et al. (2020) reported improved antibacterial activities against Staphylococcus epidermidis and P. aeruginosa of silver and gold biogenic nanoparticles from S. africana-lutea. Future research can investigate other biological activities, such as these plant-derived nanoparticles' cytotoxic, apoptotic, and anticancer activities.

Although reports from 2005 classified S. africana-lutea as a Least Concern, based on conservation status analysis, these may change as information on the biological potency broadens with more intense research. Going forward, there is a need for improved cultivation strategies for the plant to prevent its extinction. An old study by Makunga and Van Staden (2008) documented an in vitro cultivation of S. africana-lutea to produce clonal plantlets for more efficient propagation. More research efforts can be directed towards developing improved cultivation strategies as well as understanding its quantitative trait loci and genomics composition for improved breeding.