Helichrysum kraussii Sch.Bip.: Review on its medicinal uses, phytochemistry and pharmacological properties

Helichrysum kraussii Sch.Bip. is a woody shrub that naturally occurs in grasslands and woodlands in South - Central Africa. The various parts of H. kraussii serve as components used in traditional medicines within the South Central Africa region. This review provides an overview of the existing literature on the medicinal uses, phytochemical composition, and pharmacological properties of H. kraussii. The study reveals that various parts of the plant, including branches, flowers, leaves, roots, seeds, twigs, and whole plant parts, are used in ritual practices and traditional medicine to treat a range of human ailments. These include venereal diseases, nasal congestion, chest pain, skin infections, tuberculosis, respiratory infections, and cough. Phytochemical analysis of H. kraussii demonstrates the presence of acylated flavonol glucoside, diterpenes, flavonoids, phloroglucinol, and terpenoids. The pharmacological assessments indicate that crude extracts and isolated phytochemical compounds from this species possess antioxidant, antibacterial, antifungal, antiviral, cytotoxic, and anti - inflammatory activities. This mini review underscores the traditional uses, phytochemical composition, and pharmacological properties of H. kraussii . Based on the findings, it is recommended to conduct comprehensive ethno pharmacological evaluations of H. kraussii , focusing on phytochemistry, pharmacological properties, toxicological assessments, as well as in vivo and clinical research.


Introduction
Helichrysum kraussii Sch.Bip.(Fig. 1) is a well-known plant species in South Central Africa, widely used for its traditional medicinal properties (1)(2)(3).It is a perennial shrub belonging to the Asteraceae family.The genus name Helichrysum Mill.originates from the Greek words "helios" meaning "sun" and "chryson" meaning "gold," referring to the characteristic "golden flowers" of this genus (3).The species name "kraussii" is a tribute to Christian Ferdinand Friedrich Krauss, a German traveler, scientist, and plant collector who explored the Cape and Natal regions in South Africa during the 19th century (3).H. kraussii is also known by several synonyms, including H. steetzii O.Hoffm., Achyrocline batocana Oliv.& Hiern., A. steetzii (Vatke) O.Hoffm., and Gnaphalium kraussii (Sch.Bip.)Sch.Bip.(4,5).This plant species is naturally found in grasslands and woodlands in South Central Africa (Fig. 2).While considered invasive in most rangelands in Zimbabwe, H. kraussii is listed as a weed in South Africa, primarily spread by humans due to its ornamental value (6)(7)(8).The local population in South Central Africa has acquired indigenous knowledge and skills to utilize the medicinal properties of H. kraussii.Medicinal plants, their extracts, and active components derived from them play a crucial role in traditional therapy (9).Therefore, it is essential to understand the phytochemical composition of H. kraussii, as these active compounds directly or indirectly contribute to disease prevention, treatment, and overall health maintenance.Hence, this review aims to gather and summarize information on the medicinal uses, phytochemistry, and pharmacological properties of H. kraussii.
A literature search was conducted to explore the medicinal uses, phytochemistry, and pharmacological properties of Helichrysum kraussii across its distributional range in south -central Africa.Various online databases, including Scopus, JSTOR, Google Scholar, PubMed, and Science Direct, were utilized (refer to Table 1).Additionally, traditional sources like books, journal articles, dissertations, book chapters, theses, and scientific articles from the University library were consulted.To facilitate the search, keywords such as "Helichrysum kraussii," "biological activities of Helichrysum kraussii," "pharmacological properties of Helichrysum kraussii," "ethnobotany of Helichrysum kraussii," "medicinal uses of Helichrysum kraussii," "phytochemistry of Helichrysum kraussii," and "traditional uses of Helichrysum kraussii" were employed.The chemical structures of phytochemical compounds isolated from H. kraussii were depicted using the ChemSketch program.Only literature sources that evaluated the medicinal uses, phytochemistry, pharmacological, or biological activities of H. kraussii were included in this review.Excluded from this review were articles that were only partially accessed, such as abstracts, as well as published or unpublished ethnopharmacological surveys lacking information on the medicinal uses, phytochemistry, pharmacological, or biological activities of H. kraussii.

Habitat and morphology
Helichrysum kraussii, a woody shrub, reaches a maximum height of 1.5 meters (4,10).Its sturdy stems branch repeatedly (Fig. 1), displaying a brownish color.The stems are finely woolly, becoming less hairy with age, and are adorned with leaves.The leaves of H. kraussii are linear and positioned along the smaller branches.They spread out, resembling narrow needles, and have a smooth underside while being woolly and white on the upper surface.The leaves are sessile, with slightly rolled-under margins, a sharply pointed apex, and occasional fluffy galls on the branchlets.The cylindrical capitula, arranged in a corymbose manner, occur at the tips of the branches.The flowers of H. kraussii form dense terminal heads and exhibit pale yellow to straw-colored hues.This species is documented in Angola, Botswana, Eswatini, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe (5, 10) within altitudes ranging from 5 to 1850 meters above sea level (5,10).It is found in submontane grasslands, escarpment woodlands, rocky ridges on the highveld, as well as on poor soils and overgrazed land.

Ethnobotanical and ethno pharmacological uses
Helichrysum kraussii is mentioned in the monograph "Medicinal and magical plants of southern Africa: An annotated checklist" (11).It is also sold in informal herbal medicine markets in South Africa's Limpopo province (12)(13)(14) and is highly valued as a traditional medicine source.KwaZulu-Natal diviners in South Africa burn H. kraussii as  incense (15,16), and religious beliefs have ensured its careful harvesting to preserve the species.Additionally, the woolly stems of H. kraussii are used for making twig brooms in South Africa (17).Brooms are widely traded and commonly purchased by rural households instead of being made at home (17).
H. kraussii is used for traditional medicines in Eswatini, Malawi, Mozambique, South Africa, and Zimbabwe, accounting for 62.5% of the countries where the species is native (Table 2).The plant parts, including branches, flowers, leaves, roots, seeds, twigs, and whole plants, are used to treat and manage 14 human diseases and ailments in southern Africa.Crude extracts of H. kraussii are primarily used to treat venereal diseases, as indicated by a single country record and three literature sources.Other common uses include treating blocked nose and chest pains (one country record and five literature records), skin infections (one country record and six literature records), tuberculosis (one country record and 15 literature records), respiratory infections (two country records and two literature records), and as ritual and protective charms (two country records and five literature records).It is also used to alleviate coughs (two country records and 17 literature records) (Fig. 3).
H. kraussii has additional medicinal applications, such as being used as an intoxicant and pesticide, and for treating fever, headache, and temporary blindness (18)(19)(20).In combination with the leaves of Warburgia salutaris (G.Bertol.)Chiov., the leaves of H. kraussii are used as traditional medicine for asthma when taken orally as a decoction (21).When combined with the branches of Lippia javanica (Burm.f.) Spreng.and the leaves of Trichilia emetica Vahl, the branches of H. kraussii are used as a decoction to alleviate blocked nose, chest pains, and cough (22)(23)(24)(25)(26).In Zimbabwe, the roots or whole plant parts of H. kraussii are burned, mixed with salt, and taken orally as traditional medicine for coughs (1,27).While the practice of combining H. kraussii with other medicinal plants is common in south-central Africa, research on Chinese herbal medicines has shown that multi-herbal and/or drug-herbal combinations do not necessarily lead to synergistic effects (28).

Antibacterial activity
Table 4 presents the antibacterial properties of various extracts and compounds derived from H. kraussii.Kaurenoic acid, α-amyrin, β-amyrin, and essential oils obtained from H. kraussii demonstrated antibacterial effects (31,40,51,56).The acetone extracts derived from the aerial parts of H. kraussii displayed antibacterial activity (32).Antibacterial activities were observed in the chloroform: methanol extracts of H. kraussii leaves and stems (34).The ethanol extracts of H. kraussii flowers, leaves, and stems exhibited antibacterial properties (39).Moreover, water extracts from the leaves and stems of H. kraussii also showed antibacterial activity (56).

Antifungal activities
Table 5 presents the antifungal activities of various extracts and essential oils obtained from H. kraussii.The essential oils derived from the leaves and stems of H. kraussii demonstrated antifungal effects (56).Antifungal activities were also observed in the acetone extracts of the aerial parts of H. kraussii (32), as well as in the dichloromethane:methanol and aqueous extracts from the leaves and stems of the plant species (56).

Antiviral activities
The antiviral activities of H. kraussii flowers, leaves, and stems against the herpes simplex virus type-1 (HSV-1) using the cytopathic effect (CPE) inhibition assay with acyclovir as the positive control have been assessed (48).
The extract exhibited potential anti-viral activities at 50.00 μg/ml with 100% viral inhibition when tested at the highest viral dose (100TCID50), which was comparable to the antiviral activities exhibited by the positive control, which showed 100% inhibition at 1.00 μg/ml (48).In another study, the antiviral activities of acetone, dichloromethane, hexane, and methanol: water extracts of H. kraussii leaves using a colorimetric cell-based (HeLa-SXR5) assay have been evaluated (37).The acetone, dichloromethane, and hexane extracts exhibited potential anti-viral activities at 2.5 µg/ml with 97.0%HIV inhibition in the cell-based assay (37).

Anti-inflammatory activities
The anti-inflammatory activities of the flavonoid 5,6dihydroxy-3,7,8-trimethoxyflavone isolated from the flowers of H. kraussii were assessed using a cyclooxygenase-1 and -2 (COX-1 and COX-2) catalyzed reaction of the arachidonic acid-prostaglandin pathway with indomethacin as the positive control (35).The flavonoid compound exhibited prostaglandin synthesis inhibition of 54.4% and 84.7% against COX-1 and COX-2, respectively (35).Similarly, the anti-inflammatory activities of ethanol extracts of H. kraussii flowers, leaves, and stems were assessed using the COX-2 assay with ibuprofen as a positive control (48).The extract exhibited weak activities with COX-2 inhibition at 10.0 µg/ml, showing an inhibition of 57.2% compared to the 90.2% exhibited by the positive control (48).

Cytotoxicity activities
Table 6 presents the cytotoxicity activities of various extracts derived from H. kraussii.Cytotoxic effects were observed in the chloroform: methanol extract obtained from both the leaves and stems of H. kraussii (34).The flowers, leaves, and stems of H. kraussii yielded ethanol extracts that displayed cytotoxic activities (39,48).
The  (64)(65)(66).These reports align with the findings of our review, which highlight the diverse medicinal uses of H. kraussii, varying across different countries.
The treatment of respiratory infections, such as asthma, blocked nose, chest pains, cough, and tuberculosis (TB), using herbal concoctions prepared from H. kraussii, is common in south central Africa.These reports of H. kraussii's use for similar ailments and diseases in different countries call for detailed ethnopharmacological research focusing on its effectiveness and safety (38,67).Pharmacological studies on H. kraussii extracts and isolated phytochemical compounds have demonstrated various activities, including antioxidant, antibacterial, antifungal, antiviral, cytotoxicity, and anti-inflammatory effects.However, there is a lack of information on both in vitro and in vivo studies specifically examining its anti-TB activities or tests against a panel of various Mycobacteria species.Respiratory infections are a significant public health concern in south central Africa, and traditional medicines have shown great potential in their treatment and management (43,44,68,69).Therefore, it is important to understand the ethno pharmacological properties of H. kraussii extracts and phytochemical compounds isolated from the species, as these active ingredients may act directly or indirectly to prevent or treat diseases and maintain health.Evaluating the phytochemical properties of medicinal plants is essential not only to identify the main phytochemical compounds but also to gain a scientific understanding of the medicinal properties of the plant species (70).Medicinal plants like H. kraussii have been used for centuries in the treatment and management of various diseases, and their improved phytochemical profiling and ethno pharmacological research contribute to the development of current therapeutic systems.The pharmacological properties of traditional medicines depend on their primary and secondary phytochemical constituents (71).
Phytochemical compounds identified from various parts of H. kraussii include acylated flavonol glucosides, diterpenes, essential oils, flavonoids, phloroglucinol, and terpenoids (31,35,40,(49)(50)(51).Some of these secondary phytochemical constituents may be responsible for the documented biological activities of H. kraussii.Therefore, it is necessary to investigate the resulting pharmacological and toxicological properties of these phytochemical constituents in controlled clinical trials to determine their therapeutic potential and their association with specific diseases or indications related to the species.Although several phytochemical compounds have been isolated, purified, and characterized from H. kraussii, many of them still require detailed studies.So far, limited ethno pharmacological research has been conducted on the pharmacokinetics studies related to the mechanism of action of individual isolated phytochemical compounds under in vivo conditions.Ethno pharmacological research should also focus on toxicity, preclinical and clinical trials aimed at assessing the safety, effectiveness, and side effects of the phytochemical compounds in H. kraussii formulations used as traditional medicines.

Conclusion
This mini-review summarizes the medicinal use, chemical composition, and pharmacological properties of H. kraussii.Such studies are crucial for plants commonly employed in traditional medicine, as they allow for the assessment of their phytochemistry, pharmacology, and toxicology.Notably, various phytochemical compounds have been isolated from H. kraussii, including acylated flavonol glucosides, diterpenes, essential oils, flavonoids, phloroglucinol, and terpenoids.These compounds have exhibited antibacterial, anti-inflammatory, and antioxidant activities.However, it is important to note that these studies are preliminary, and further ethno pharmacological research is needed.This research should focus on comprehensive evaluations, safety assessments, in vivo mechanisms of action, and clinical investigations to validate the traditional medicinal applications of H. kraussii.Due to the variations in phytochemical constituents depending on the origin and plant parts, it is crucial to establish a standardized phytochemical profiling protocol to isolate and obtain pure compounds from H. kraussii.Additionally, considering the diverse mechanisms of action exhibited by the phytochemical compounds mentioned in this review, future studies should prioritize the assessment of toxicity and safety using animal models.

Figure 3 .
Figure 3. Main diseases and ailments treated and managed by Helichrysum kraussii in south tropical Africa

Table 1 .
Website links for all databases used in this study

Table 5 .
Summary of antifungal activities of the extracts and essential oils isolated from different parts of Helichrysum kraussii

Table 4 .
Summary of antibacterial activities of the extracts and compounds isolated from different parts of Helichrysum kraussii present review aims to provide comprehensive information on the medicinal uses, phytochemistry, biological activities, and botany of H. kraussii, encompassing literature published from 1962 to 2023 (34).H. kraussii is a member of the Helichrysum genus, which is widely utilized as a source of traditional medicines in southern Africa.Other species within this genus, such as H. caespititium (DC.)Harv., H. cymosum (L.) D.Don ex G.Don, H. longifolium DC., H. nudifolium (L.) Less., H. odoratissimum (L.) Sweet, H. pedunculatum Hilliard & B.L. Burtt, and H. petiolare Hilliard & B.L. Burtt, have also been documented for their medicinal properties (57-63).Some of these Helichrysum species, including H. nudifolium and H. odoratissimum, have commercial potential as ritual incense, sedatives, and herbal remedies in southern Africa, particularly for colds and chest pains.Additionally, their essential oils exhibit commercial potential for inhalation and aromatherapy purposes

Table 6 .
Summary of cytotoxicity activities of the extracts isolated from different parts of Helichrysum kraussii