Sustainable Applications of Endophytic Bacteria and Their Physiological/Biochemical Roles on Medicinal and Herbal Plants: Review

Bacterial endophytes reside within the tissues of living plant species without causing any harm or disease to their hosts. These endophytes can be isolated, identified, characterized, and used as biofertilizers. Moreover, bacterial endophytes increase the plants’ resistance against diseases, pests, and parasites, and are a promising source of pharmaceutically important bioactives. For instance, the production of antibiotics, auxins, biosurfactants, cytokinin’s, ethylene, enzymes, gibberellins, nitric oxide organic acids, osmolytes, and siderophores is accredited to the existence of various bacterial strains. Thus, this manuscript intends to review the sustainable applications of endophytic bacteria to promote the growth, development, and chemical integrity of medicinal and herbal plants, as well as their role in plant physiology. The study of the importance of bacterial endophytes in the suppression of diseases in medicinal and herbal plants is crucial and a promising area of future investigation.


Introduction
It is well known that users of endophytic bacteria employ comparable strategies to enhance plants growth. In addition, endophytic bacteria are more successful than rhizobacteria at reducing the negative impacts of environmental stressors on plants. They enter the plant tissue primarily through the roots and other natural openings in the plant. After entering the plant, bacterial endophytes may spread throughout the tissues of the host plant [1]. Medicinal and herbal plants have secondary metabolites which function as important drugs, flavor, fragrances, agrochemicals, dye, pigments, pesticides, and may play a key role in the adaptation of plants to their environment [2].
Bacterial endophytes of the genera Bacillus, Pantoea, Pseudomonas, Stenotrophomonas, and Serratia can produce phytohormones, such as auxin and gibberellin, as well as protease and hydrogen cyanide, and play a role in siderophore production, phosphate solubilization, and atmospheric nitrogen fixation [3]. Among other endophytes, Bacillus, Pseudomonas, Agrobacterium, and Flavobacterium species solubilize the inorganic phosphate compounds by phosphatases. Bacterial species of the genera Alcaligenes, Arthrobacter, Azotobacter, Bradyrhizobium, Chromobacterium, Enterobacter, Escherichia, Micrococcus, Streptomyces, Serratia, and Thiobacillus secrete organic acids to solubilize the insoluble phosphorus. Pseudomonas spp. and Bacillus spp. are known endophytes that are involved in siderophores production [4]. For example, secondary metabolites produced by endophytic bacterium Bacillus pumilus have a significant inhibitory effect against fungal species, such as Pythium aphanidermatum, Rhizoctonia solani, and Sclerotium rolfsii [5]. The leaf and stem of heart-leaved moonseed (Tinospora cordifolia (Thunb.) Miers) contain Bacillus, Aneurinibacillus, and Pseudomonas species [6]. Traditional medicine has long utilized T. cordifolia to treat several conditions including fever, jaundice, chronic diarrhea, cancer, dysentery, bone fractures, pain, asthma, skin diseases, deadly bug bites, and eye issues.
Nitrogen-fixing bacterial strains are linked with certain leguminous and non-leguminous species [7]. Species such as Gluconacetobacter diazotrophicus and Azorhizobium caulinodans can fix nitrogen [8]. Pseudomonas putida, Azospirillum brasilense, and Enterobacter cloacae enable plants to grow and survive under higher levels of polyaromatic hydrocarbons (PAHs) through phytoremediation [9]. Arthrobacter sp. and Bacillus sp. bacterial endophytes produce secondary metabolites for plants to adapt to abiotic stress [10]. Several studies have shown that endophytic bacteria play a beneficial role in plant growth. It is not yet clear which bacterial strains contribute more to the growth and development of medicinal plants. It is well-known that the density of endophytic bacteria within the plant tissues is less than that of found in the rooting zone [11]. Plant-growth-promoting (PGP) bacteria that fix nitrogen may be used as biofertilizers to improve plant growth [12]. Many of these bacteria also produce phytohormones [13]-for example, as the bacterial strain SCCPVE07-that improve the growth of coriander (Coriandrum sativum L.) grown under salinity stress [14]. The stem and leaves of coriander have antimicrobial and antibacterial qualities. Inoculated C. sativum showed higher levels of calcium, carbon, iron, and potassium contents. In this case, the levels of cinnamic acid, 4-methoxy-cinnamic acid hexoside, 5-O-caffeoylquinic acid, K-3-O-rutinoside, Q-3-O-rutinoside, Q-3-O-glucoside, and Q-3-O-glucuronide were significantly increased [15]. In addition, certain plant species are capable of accumulating heavy metals and soil contaminants in their tissues [16].
In this context, we aim to provide a review of the sustainable applications of endophytic bacteria and their physiological and biochemical processes on m medicinal and herbal plants to lay a foundation for future studies intended for the isolation, identification, and characterization of endophytic bacteria from the internal tissues of medicinal and herbal plants. Understanding these functions might lead to the development of new techniques in agricultural and biotechnological environments, specifically for the future cultivation and commercialization of indigenous medicinal and herbal plants.

Potentialities of Endophytic Bacteria
In this regard, this research thoroughly examines several bacterial endophytes and their potentialities on herbal plant species without inflicting any harm or disease to their hosts, drawing on a variety of sources in the literature. These endophytes can be isolated, recognized, and characterized in addition to being employed as biofertilizers to improve plant development and change the chemical makeup of the plant. Additionally, bacterial endophytes boost plants' resilience to diseases, pests, and parasites and are a promising source of bioactives with the potential for use in pharmaceuticals ( Figure 1). For instance, the existence of distinct bacterial strains is credited with the synthesis of antibiotics, auxins, biosurfactants, cytokinins, ethylene, enzymes, gibberellins, nitric oxide organic acids, osmolytes, and siderophores. In order to enhance the growth, development, and chemical integrity of medicinal and herbal plants, as well as their function in plant physiology, this manuscript reviews sustainable applications of endophytic bacteria. It is critical to examine the role of bacterial endophytes in the control of illnesses in medicinal and herbal plants-a promising avenue of future research.

Growth-Promoting through Nitrogen Fixation, Phosphate Solubilization and Anti-Pathogenic Capabilities
Endophytic bacteria have been increasingly associated with the ability to suppress a broad pool of plants diseases, with this ability being closely associated with the vegetative growth and chemical composition of the plant [17]. Different alkaloids contribute to plant defense through endophytes action, acting as growth-promoting compounds or having a key role in plants' resistance to environmental stress. Amines and amides, very common metabolites from endophytes, present toxic activities against insects. Steroids, terpenoids, and diterpenes are also generated by endophytes [18] and are responsible of several activities such as plant-growth promotion and yield, suppression of pathogengrowth and colonization, contaminants remotion, phosphate solubilization, and nitrogen plant-assimilation [19]. These properties may be helpful in organic tea plantation [20,21].
Pseudomonas and Bacillus spp. were studied for their role against blister blight disease P. fluorescens BCA08 reduced the growth rate and disease incidence of the causal agent of anthracnose Colletotrichum higginsianum [61]. The endophyte B. subtilis ALB629 isolated from cacao seedlings has antimicrobial properties against fungi Moniliophthora perniciosa and Colletotrichum gossypii. B. subtilis ALB629 promotes growth of both the aerial and roots of cacao seedlings [62]. 16S rRNA sequence analysis revealed Bacillus, Streptomyces, Pseudovibrio, and Pseudomonas species isolated from Rhizophora stylosa. These isolates had antimicrobial activity against E. coli ATCC 25922, P. aeruginosa ATCC 25923, B. subtilis ATCC 27212, S. aureus ATCC 12,222, and C. albicans ATCC 7754 [63].
Dendrobium spp. are medicinal plants containing properties with anti-cancer, antifatigue, gastric ulcer protective effects, etc. Of all the bacterial endophytes isolated from stems of Dendrobium spp. plants, Bacillus megaterium exhibited the highest antimicrobial effects [64]. Acinetobacter guillouiae, B. cereus, Burkholderia tropica, Novosphingobium sp., Pseudomonas moraviensis, Pseudomonas sp., Rahnella aquatilis, and Raoultella ornithinolytica, were isolated from the Cape coast lily (Crinum macowanii Baker) bulbs and showed potential for possible drug lead against common pathogenic bacteria [65]. Traditional uses of C. macowanii include treating boils, diarrhea, fever, inflammation, respiratory issues, skin rashes, tuberculosis, wounds, and urinary tract issues. Bacterial isolates FjR1 and FjF2 from the Indian coffee plum (Flacourtia jangomas (Lour.) Raeusch.) displayed potential antimicrobial activity against pathogenic bacteria [66]. The longevity spinach (Gynura procumbens DC.) is a medicinal plant species for treatment of cancer, constipation, fever, kidney diseases, rheumatism, rashes, headache, and viral skin diseases [67,68]. The leaves of G. procumbens contain anti-herpes simplex virus, antihyperglycemic, anti-inflammatory, antihyperlipidemic, anti-allergy agent, and antihypertensive properties [68]. Apart from its antihypertensive, glucose-lowering, and anti-inflammatory properties, it is also a source of proteins and peroxidase [69]. G. procumbens leaves contain essential oil, flavonoids, miraculin, polyphenols, peroxidase, thaumatin-like proteins, terpenoids, and unsaturated sterols. The screening of endophytic bacteria for the plant growth regulators such as cytokinin were needed as means to explore if these endophytic bacteria can be applied in agriculture [67]. Acenitobacter calcoaceticus, Paenibacillus polymaxa, and Psuedomonas resinovorans were isolated from G. procumbens leaves collected in Malaysia [68]. It was also found that broth extracts from P. resinovorans and P. polymaxa contain cytokinin-like compounds [68].
Acetone extract from kauri booti (Ajuga bracteosa Wall ex Benth.) has antibacterial activity against E. coli [70]. This plant contains phytochemicals which have anti-inflammatory, astringent, diuretic, and depurative properties, and can be used to treat agues, menorrhea, bronchitis, diarrhea, fever, gout, jaundice, pneumonia, palsy, and rheumatism [71]. The leaves, bark, stem, and roots of A. bracteosa have medicinal properties, can be used as an astringent against hypoglycaemic and gastrointestinal disorders, and have anthelmintic, diuretic, antifungal, anti-inflammatory, and antimycobacterial compounds [71]. Bacterial species were isolated and screened for PGP and biotechnological potential associated with A. bracteosa, with most isolates belonged to Proteobacteria and Pseudomonas [70,71]. These isolates exhibited PGP through production of siderophores and indole acetic acid. They are also capable of phosphate solubilization through production of hydrolytic enzymes such as amylase, cellulose, chitinase, lipase, pectinase, phosphatase, and protease [71].
The biological compounds produced by endophytic bacteria play a pivotal role in the protection of medicinal and herbal plants against pests and pathogens (Table 1). Living plants are a good source for bacterial endophytes which can be isolated for more efficient production of antimicrobial compounds with pharmacological importance. In turn, medicinal plants could also benefit in terms of growth promotion with less application of inputs such as fertilizers, fungicides, insecticides, or herbicides.

Growth-Promoting Bacteria on Medicinal and Herbal Plants
Sixty-one bacteria were identified and comparatively characterized from the root nodules of Medicago, Melilotus Onobrychis, Oxytropis, and Vicia species grown in the Loess Plateau and Qinghai-Tibet Plateau [100]. Vicia sativa has been used as a traditional medicine to treat asthma, bronchitis, skin infections, and urinary diseases, and it also has anti-poison, antiseptic, aphrodisiac, antipyretic, and antirheumatic properties [101]. Oxytropis spp. contain flavonoids, alkaloids, and saponins which have medicinal properties [102]. Apigenin, caffeic acid, gallic acid, pyrogallol, salicylic acid, naringenin, quercetin, myricetin, and daidzein are major secondary metabolites in the extract of the alfalfa (Medicago sativa L.) leaves [103]. Melilotus spp. are native to the Mediterranean area [104]; their herbs have aromatic, emollient, and carminative properties [105]. Onobrychis genus is an important legume with over 150 species [106]. Among the bacterial isolates are Rhizobium leguminosarum, S. meliloti, and S. fredii; the rest belong to Mesorhizobium, Phyllobacterium, and Stenotrophomonas. Species of R. leguminosarum was isolated from Oxytropis spp. and medick or burclover (Medicago archiducis-nicolai Širj.), while S. fredii was isolated from the black medick (Medicago lupulina L.) grown in the Qinghai-Tibet Plateau. These strains were also found to be resistant to high alkalinity and a high concentration of NaCl [100]. V. sativa contains significant activity against pathogenic bacterial species such as Bacillus atrophaeus, E. coli, S. aureus, and Staphylococcus epidermidis [101]. Medicago spp. are used to treat eczema, anemia, constipation, body odor, infections, burns, athlete's foot, cancer, arthritis, intestinal ulcers, gastritis, liver diseases, bleeding gums, and high blood pressure.
The hyacinth bean (Lablab purpureus (L.)) serves as a herbal medicine in China for the treatment of internal heat fever. The leaves and fruits of L. purpureus contain sterols and fatty acids such as palmitic, palmitoleic, linoleic, and linolenic acids [104,107,108]. Pyridine alkaloids, trigonelline, and sterols have been isolated from tissue cultures of seeds, stems, and leaves. To study the diverse rhizobia associated with this plant, Bradyrhizobium, Rhizobium, Ensifer, and Mesorhizobium species were isolated from southern China [104].
Based on 16S rDNA analysis, the bacteria isolated belonged to Aeromonas, Bacteroides. Cytophaga, Flexibacter, Ilyobacter, Pelomonas, Proteobacteria, Pseudomonas, Rhodoferax, Rhizobium, Sulfurospirillum, and Uliginosibacterium. These endophytic bacteria have the capacities of fixing nitrogen and removal of contaminants from the water body through phytoremediation by degrading catechol, cyanide, methane, methanol, methylated amines, oxochlorate, urea, and 2,4-Dichlorophenoxyacetic acid [109]. Although this area of study will not form part of our investigation, we may opportunistically assess the possibility of environmental remediation by bacteria when we survey natural populations of A. phylicoides.
Caragana spp. are leguminous plants containing more than 80 species worldwide [110]. The roots, flowers, shoots, barks, and seeds are useful plant parts applied as herbal medicine [111] for the treatment of cancer of gynecological problems [112]. Species of the genus Caragana are resistant to extreme temperatures and have nitrogen-fixing abilities [110]. Agrobacterium, Mesorhizobium, Rhizobium, Bradyrhizobium, and Phyllobacterium species are associated with Caragana species grown in China [110].
Sinorhizobium morelense sp. nov. isolated from root nodules of jumbay (Leucaena leucocephala (Lam.) de Wit) has been found to be resistant to carbenicillin, kanamycin, and erythromycin [125]. This medicinal plant is frequently used to treat diabetes. It is also used to treat stomach ailments, assist abortion, and promote contraction. The revealed Allorhizobium undicola sp. nov. solated from the water mimosa or sensitive Neptunia (Neptunia natans (Girard) Kuntze) based on the 16S rRNA gene sequencing has nitrogen-fixing ability [126]. This medicinal plant has pharmacological qualities that include antifungal, antiemetic, astringent, anthelmintic, antidysentery, diuretic, anti-inflammatory, antioxidant, hypercholesterolemia, antipyretic, and antiemetic properties.
From nodules of False Indigo (Amorpha fruticose L.), M. amorphae sp. nov was characterized based on the RFLP of PCR-amplified 16S rRNA genes, MLEE, DNA-DNA hybridization, 16S rRNA gene sequencing, electrophoretic plasmid profiles, cross-nodulation, and a phenotypic study [127]. A. fruticose is used to treat dermatitis, carbuncles, and burns in traditional Chinese medicine. DNA-DNA hybridizations were conducted to identify Mesorhizobium spp. from the sample from the white carob tree (Prosopis alba Griseb.) root nodules grown in Argentina [128]. R. tropici were found to be root modulating bacteria of N. natans from India [129]. Prosopis plants have a variety of bioactive qualities, including antioxidant, anti-inflammatory, anti-cancer, and anti-diabetic properties.
A new species name for a root-forming nodule bacterial isolate, Devosia neptuniae sp. nov., which was previously classified as A. undicola, was suggested to neptuniummodulating rhizobia isolated from India. This bacterial species can form a bonafide dinitrogen-fixing root-nodule symbiosis with other legume plants [130].
Root-nodule isolates of Bradyrhizobium, Mesorhizobium, Rhizobium, and Sinorhizobium spp. from Lespedeza spp., collected from China and the USA, were isolated and characterized using SDS-PAGE analysis of whole-cell proteins, DNA-DNA hybridization, and 16S rRNA gene sequence analysis [131]. Ralstonia taiwanensis sp. nov. was isolated from Mimosa spp. and is the capable of root nodule formation and nitrogen fixation [132].
The endophytic bacterial isolates from H. carnosum, H. spinosissimum subsp. capitatum, and H. pallidum grown in Algeria were identified as P. agglomerans, E. kobei, E. cloacae, L. adecarboxylata, E. vulneris, and Pseudomonas sp. by means of ARDRA using the enzyme Cfo I, RAPD fingerprinting and sequencing of 16S rDNA. This was the first report confirming that Gammaproteobacteria is associated with H. carnosum, H. spinosissimum subsp. Capitatum, and H. pallidu [117]. The diversity of endophytic bacteria from the root of Angelica sinensis in Angelica in the Gansu province revealed that certain endophytic bacterial strains may have come from the rooting zone [133].
Among the endophytic bacteria isolated from the red clover (Trifolium pratense L.), P. agglomerans (59.6%) was mostly detected in foliage tissues, Agrobacterium rhizogenes A in the tap root (49.2%), and R. leguminosarum BV phaseoli and R. loti B in the nodules (27.2% each) [134]. In addition, T. pratense has been used medicinally to treat a number of illnesses, such as eczema and psoriasis, cancer, whooping cough, respiratory issues, and skin inflammations. B. megaterium, Bordetella avium, Curtobacterium luteum, and R. leguminosarum BV trifolii promoted the growth of T. pratense. Nodulation of red clover seedlings became evident because of co-inoculation of R. leguminosarum BV trifolii with Bacillus insolitus, B. brevis, or A. rhizogenes A [134]. Crop rotations of T. pratense and potato (Solanum tuberosum L.) have specific associations with bacterial endophytes. Of all the growth-promoting bacterial strains isolated from these plants, 63% enhanced shoot height, 66% enhanced shoot wet weight, and 55% enhanced root wet weight [135]. It has been claimed that potatoes offer a multitude of medicinal properties, including antioxidant, anticancer, antiallergy, antibacterial, anti-inflammatory, anti-obesity, and anti-ulcer action. A total of 200 bacterial isolates from the berseem clover (Trifolium alexandrinum L.) possess plant growth promoting traits. Production of indole acetic acid by the endophytic bacteria stimulated the plant development of rice plant [136]. Because of their expectorant, analgesic, and antibacterial qualities, Trifolium spp. are also used to treat rheumatic pains. Coinoculation of T. repens with Rhizobium strains CHB1120 and CHB1121, Bacillus aryabhattai strain Sb, and A. vinelandii strain G31 promotes the nitrogen fixation and nutrient uptake of white clover in a P-deficient soil [137].
Nitrogen-fixing bacteria can form endophytic colonies in various medicinal and herbal plants. These beneficial bacteria fix nitrogen from the atmosphere to enhance the length and biomass of medicinal and herbal plants. Nitrogen-fixing endophytic bacteria may be useful for the sustainable production of medicinal and herbal plants, specifically in saline-based environments. Nitrogen-fixing bacteria are currently being introduced as biofertilizers.
The study revealed beneficial effects on the dry weight, P assimilation, and barley yield in E. ludwigii-inoculated plants [138]. C. nepeta, M. communis, M. officinalis, and L. stoechas produce essential oils Interestingly, aromatic plants are more colonized than the other species, whereas the non-woody perennials are more highly colonized than the water pepper (Polygonum hydropiper (L.) Delabre 1800) is regarded as a P-accumulating herb used for P-phytoextraction, with higher P-accumulating capability in the mining ecotype compared to the non-mining ecotype [139]. In traditional medical systems, water pepper is used as an astringent, sedative, antiseptic, and to treat respiratory problems, edema, and snake bites.
Aloe (Aloe barbadensis Mill.) is an important medicinal plant with applications in pharmaceutical, food, and cosmetic industries and is used for flavoring liquid formulations [154]. A. barbadensis contains phenolic compounds such as aloin-A (barbaloin), aloesin, soaloeresin D, and aloeresin E used in the treatment of tumors, diabetes, ulcers, and cancer [155]. Burkholderia gladioli, Enterobacter hormaechei, Pseudomonas synxantha, and S. marcescens isolated from A. barbadensis are capable of solubilizing phosphate into liquid phase [154]. From Brassica juncea (L). Czern and Coss var. Pusa Bold (DIR-50), a Ni-tolerant B. subtilis strain SJ-101 was isolated and identified. It was found that the strain SJ-101 produced indole acetic acid and solubilized inorganic phosphate [55]. Endophytic bacteria isolate from P. hydropiper contains plant growth promotion traits including indole acetic acid, siderophores, and phosphate-solubilization among others [156]. Endophytic bacterial strains isolated from the tissues of livening thyme (Thymus vulgaris L.) exhibited some plant growth-promoting activities such as auxin synthesis, diazotrophic, P-solubilization, siderophore production, and production of lytic enzymes (i.e., chitinase, cellulase, protease, and lipase) under in vitro conditions [157]. T. vulgaris has been used for treating chest congestion and promoting salivation since ancient times. The fresh leaves are also consumed to soothe sore throats.
Endophytic bacteria are capable of solubilizing inorganic phosphate in a solid medium, thereby increasing its availability to living medicinal and herbal plants ( Table 2). Phytochemicals released by endophytic bacteria promote the sustainable production of medicinal and herbal plants resulting from improved fertility of the soil, and hence increase medicinal and herbal plant production.

Endophytic Bacterial Species Responsible for Phytomediation on Medicinal/Herbal Plants
Due to a variety of industrial activities as well as natural processes, the accumulation of heavy metals in soil has rapidly grown. Endophytic bacteria can be isolated from leaves, stems, and roots of plants grown in contaminated soil. Many endophytes are capable of degrading organic contaminants and heavy metals, and can therefore be used for phytoremediation on contaminated soils [175]. The mobility and bioavailability of heavy metals in the soil influence phytoextraction and phytostabilization [16,155]. Plant tolerance to the contamination is crucial for successful phytoremediation [176]. Decontamination may be accelerated with appropriate microorganisms' inoculation that is able to break down pollutants and compete with indigenous microorganisms.
Yellowtop (Alyssum murale Waldst. and amp; Kit.) is regarded as a metal hyperaccumulator plant and is able to solubilize Ni. A. murale has been used in combination with other medicinal plants for gynecological disorders. It has also been found that Microbacterium oxydans AY509223 increased Ni uptake of A. murale [177]. NBRI K28 Enterobacter sp. also has aminocyclopropane-1-carboxylic acid deaminase activity and increased the growth of the brown mustard (Brassica juncea (L.) Czern.) plants. NBRI K28 Enterobacter sp. enhanced phytoextraction of metals of Ni, Zn, and Cr accumulated by B. juncea [178,179]. P. putida strain PS9, isolated from the turnip (Brassica campestris L.), solubilized phosphate and produced significant amount of salicylic acid, 2,3-dihydroxy benzoic acid, and indole acetic acid [180]. Antioxidant, antibacterial, and anticancer properties are present in Brassica spp.
A considerable number of bacterial strains have been isolated from heavy metalpolluted soil in Nanjing, China, which promoted plant growth and cadmium uptake in rape [Brassica napus L.) [181]. Some of these bacterial isolates had the potential to solubilize cadmium carbonate in solution culture. It has been also confirmed that these cadmiumresistant isolates exhibit the presence of indole acetic acid. These bacterial isolates colonized and developed in B. napus after root inoculation [181]. P. fluorescens G10 and Microbacterium sp. G16 were isolated and identified by means of 16S rDNA gene sequence analysis from the roots of B. napus grown in Pb-contaminated soils. There was significant increase in root elongation of inoculated B. napus seedlings. Endophytic bacterium JN6 isolated from roots of the drooping knotweed (Polygonum pubescens Blume) was identified as Rahnella sp. This showed very high Cd, Pb, and Zn tolerance and effectively solubilized CdCO3, PbCO3, and Zn3(PO4)2 in culture solution [10]. Microbacterium sp. G16 produced indole acetic acid, siderophores, and 1-amino cyclopropane-1-carboxylate deaminase [181]. It has been demonstrated that P. pubescens works well as a traditional Chinese medicine. The Proteobacteria, Actinobacteria, and Bacteroidetes Chloropid isolated from the goat willow (Salix caprea L.) were resistant to Zn/Cd as they produced aminocyclopropane-1-carboxylic acid deaminase, indole acetic acid, and siderophores [182]. The leaves S. caprea are made into a decoction which is used to cure fevers. The isolated Bradyrhizobium sp. (vigna) RM8 from nodules of V. radiata sampled from nickel and zinc in India promoted the growth of the host plant [183]. This was evidently shown by the increase in nodule numbers, leghaemoglobin, seed yield, grain protein, root N, and shoots.
Using HPLC analysis, Enterobacter sp. was isolated from the long-stamen onion (Allium macrostemon Bunge) plants grown in polycyclic aromatic hydrocarbon-contaminated soils [184]. This bacterial species also promoted the growth of wheat and maize and removed pyrene from pyrene-amended soil in pot experiments. Enterobacter sp. produced indole acetic acid, siderophore, and solubilize inorganic phosphate. A. macrostemon has historically been used to alleviate thoracic pain, stenocardia, heart asthma, and diarrhea. Bacillus sp., isolated from the roots of venboksal (Alnus firma Siebold and Zucc.) using 16S rRNA sequence analysis, demonstrated the capacity to produce siderophores and indole acetic acid. There was increased root elongation of inoculated B. napus seedlings [185]. The isolates facilitated the capability of reducing heavy metal phytotoxicity and increasing Pb accumulation in A. firma. Alnus spp. are well recognized for their traditional medical uses, which include treating conditions including cancer, hepatitis, uterine cancer, rheumatism, and dysentery, as well as causing stomachaches, diarrhea, and fever. The bacterial population associated with T. caerulescens subsp. calaminare sampled had Zn and Cd capabilities due to the increased availability of the metals in soils near the roots [186]. Based on 16S rRNA sequence analysis, Methylobacterium spp., Rhodococcus spp., and Okibacterium spp. were isolated from the pennycress (Thlaspi goesingense Halácsy) accumulated Ni in ultramafic soils. These isolates produced 1-amino cyclopropane-1-carboxylic acid deaminase and siderophore [187]. Four groups of heavy metal-resistant bacterial such as Actinobacteria, Proteobacteria, Bacteroidetes, and Firmicutes were isolated from the roots, stems, and leaves of black nightshade (Solanum nigrum L.) [188]. These isolates were re-inoculated into S. nigrum under Cd stress which resulted in Cd phytotoxicity decrease. S. nigrum has historically been used to treat bacterial infections, coughs, and indigestion. An endophytic bacteria Serratia sp. RSC-14 isolated from the roots of S. nigrum displayed phosphate solubilization and produced indole acetic acid [189].
Endophytic bacteria associated with the roots, stems, and leaves of Alyssum bertolonii Desv. sampled from central Italy influenced plant growth [190]. These endophytic bacteria also shown potential for nickel-hyperaccumulation There was significant increase in biomass and metal accumulation. Cupriavidus taiwanensis TJ208 isolated from the bashful (Mimosa pudica L.) removed Pb, Cu, and Cd from polluted soils [191]. Since ancient times, M. pudica has been administered topically to heal wounds as well as urogenital disorders, piles, dysentery, and sinuses. Bacillus thuringiensis GDB-1 enhanced growth of A. firma, through production of aminocyclopropane-1-carboxylic acid deaminase activity, indole acetic acid, and siderophores; as well as P solubilization. B. thuringiensis GDB-1 also accumulated As, Cu, Pb, Ni, and Zn in seedlings of A. firma [192]. Zn-tolerant bacterial strains such as B. subtilis, B. cereus, Flavobacterium sp., and P. aeruginosa, isolated from the Chinese violet cress (Orychophragmus violaceus (L.)), significantly increased the shoot biomass and Zn accumulation in O. violaceus [3]. On the other hand, B. subtilis, B. cereus, B. megaterium, and P. aeruginosa isolated from O. violaceus significantly enhanced growth plant and Cd accumulation [193]. O. violaceus oil can be used to make a variety of cosmetic products for the care of the skin, hair, and lips, as well as to make external preparations for the treatment of burns. The diversity of endophytic bacteria associated with the root, stem, and leaf of Poplus sp. enhanced phytoremediation on localities contaminated with BTEX compounds [194].
Root-colonizing beneficial bacteria can improve plant growth through resistance to biotic and abiotic stresses. Drought is an environmental condition affecting the productivity of medicinal plants globally. PGP rhizobacteria produce secondary metabolites that could relief drought stress in plants [201]. Pseudomonas pseudoalcaligenes and B. pumilus have a significant ability to withstand adverse effects caused by saline stress [202].
A. linearis and Cyclopia spp. are South African indigenous herbal leguminous species grown in acidic soils. Among the rhizobial isolates from root nodules of A. 24spalathus and Cyclopia spp., bacterial species of genera Rhizobium, Burkholderia, Mesorhizobium, and Bradyrhizobium produce bioactive compounds that affect the growth of leguminous plants [58].
A heavy-metal-resistant strain of Bacillus edaphicus NBT was evaluated on B. juncea for its plant growth promotion. B. edaphicus NBT produced indole acetic acid, siderophores, and aminocyclopropane-1-carboxylic acid deaminase. There was also an increase in Pb uptake by B. juncea inoculated with B. edaphicus NBT [208]. In pot experiments, 16S rDNA sequencing identified E. aerogenes and R. aquatilis isolated from B. juncea. These isolates stimulated the growth of B. juncea exposed to environments contaminated with Ni and Cr [209]. These bacteria also produced siderophores, aminocyclopropane-1-carboxylic acid deaminase, indole acetic acid, and phosphate solubilization [209]. B. pumilus (STR2) and Exiguobacterium oxidotolerans (STR36) promoted the growth of the water hyssop (Bacopa monnieri (L.) Pennell) grown in salt-stressed soils, enhanced proline levels and decreased lipid peroxidation [76]. Traditional medicine from B. monnieri may improve cognitive performance, cure ADHD symptoms, and lessen stress and anxiety.
The jute mallow or nalta jute (Corchorus olitorius L.) inoculated with P. extremorientalis TSAU6, indole acetic acid, and gibberellic acid exhibited a significant increase in root length, shoot length, and fresh weight, indicating that plant growth regulators such as auxins and gibberellins play an important role in plant salinity tolerance [59]. C. olitorius is a leafy vegetable that is frequently used in soup recipes and traditional medicine to treat tumors, chronic cystitis, and fever. B. megaterium MTCC446 isolated from gale of the wind (Phyllanthus amarus Schumach. and Thonn.) promoted a higher vigor index, germination (%), plant biomass, P content, plant phenolic content, radical scavenging, and antioxidant activity [60]. P. amarus is frequently used in African traditional medicine to treat a variety of illnesses, including kidney stones, dysentery, jaundice, diarrhea, and urogenital problems.
Under the pot experiment, Achromobacter xylosoxidans isolated from the bright eyes (Catharanthus roseus (L.) G. Don) exposed to saline soils in Tamilnadu, India, produced aminocyclopropane-1-carboxylic acid deaminase [210]. C. roseus is a significant medicinal plant that is found around the world. It contains a variety of phytochemicals that have biological effects (antioxidant, antibacterial, antifungal, and anticancer). Under drought conditions, the ringed lavender (Lavandula dentata L.) isolates of B. thuringiensis increased plant growth and nutrition. B. thuringiensis produced indole acetic acid and aminocyclopropane-1-carboxylic acid deaminase and solubilized P, demonstrating its capacity to enhance plant growth under stress conditions [102]. In traditional medicine, L. dentata has been used to cure rheumatism, headaches, colds, and the flu.
Environmental contamination became a major challenge in recent decades due to rapid industrialization in developed countries. Mining activities, wastewater discharge, volcanic eruptions, and rock weathering affected the growth and productivity of soil. Endophytic bacterial species could be a potential mechanism in phytoremediation strategies for the management of environmental contaminants, while plants benefit through growth promotion (Table 3).

Conclusions
The sustainable production of medicinal and herbal plants has been one of the major challenges facing agriculture in recent years, with the ongoing over-utilization of chemicals to meet the population demands. To solve these problems, an environmentally friendly way forward focusing on the minimal usage of agrochemicals is require. Endophytic bacterial isolates could be a potential source of phytochemical compounds to enhance plant production. In addition, endophytic bacteria enable the plant species to resist abiotic stress conditions. Endophytic bacterial living in plant tissues produce plant growth-promoting compounds such as phytohormones; enzymes such as Aminocyclopropane-1-carboxylic acid deaminase, which reduce the levels of ethylene; organic acids aiding in P solubilization; and siderophores, cellulases, and chitinases inhibiting the phytopathogens growth. Sustainable agriculture provides a platform to medicinal and herbal plant producers from which to apply new agricultural techniques and biotechnologies to enhance plant growth by using bacterial isolates as biofertilizers. The modes of actions of several endophytic bacterial species have been well documented; they are recognised as plant growth promotion agents based on other biochemical and physiological attributes such as biological nitrogen fixation, phosphate solubilization, siderophore production, and the synthesis of PGP substances. In addition to improving plant nutrient availability and providing protection against varied abiotic and biotic stresses, endophytic bacteria play a pivotal role in enhancing medicinal and herbal plant productivity while simultaneously ensuring the sustainable maintenance of soil health.

Conflicts of Interest:
The authors declare no conflict of interest.